CD4-SPECIFIC ANTIBODY CONSTRUCTS AND COMPOSITIONS AND USES THEREOF

Description

FIELD

The present disclosure relates to antibodies or antigen binding fragments thereof that specifically bind human CD4. Also disclosed are fusion proteins comprising an envelope glycoprotein G, H, HN, and/or an F protein of the Paramyxoviridae family. Also disclosed are fusosomes comprising an envelope glycoprotein G, H, and/or an F protein of the Paramyxoviridae family. Fusosomes in one embodiment are gene therapy vectors pseudotyped with an envelope glycoprotein, including envelope glycoproteins G, H, HN and/or an F protein of the Paramyxoviridae family. Also disclosed are an envelope glycoprotein G, H, HN, and/or an F protein of the Paramyxoviridae family and a CD4 antibody, or an antigen binding fragment thereof, for targeting and transducing cells expressing CD4. Viral vectors and other compositions containing the fusion proteins, antibodies, or antigen binding fragments thereof, as well as methods of using the fusosomes, fusion proteins, antibodies, or antigen binding fragments thereof are also disclosed.

SUMMARY

CD4 (cluster of differentiation 4) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR). CD4 serves multiple functions in immune responses against both external and internal challenges. In T cells, the CD4 co-receptor functions primarily to bind to a major histocompatibility complex (MHC) molecule to facilitate T cell signaling and aid with cytotoxic T cell antigen interactions. While CD4 is predominantly expressed on the surface of helper T cells, it can also be found on natural killer cells, cortical thymocytes, and dendritic cells. The CD4 molecule is also used as a marker for cytotoxic T cell populations.

T lymphocytes are common targets in gene therapy, even more so since chimeric antigen receptor (CAR) T cells have reached the clinic. Current approaches for T cell engineering mainly rely on ex vivo gene transfer methods. Following their isolation from either healthy donors or patients, lymphocytes are activated and subsequently transduced by lentiviral vectors. The modified lymphocytes are then expanded and either used in functional in vivo assays or used for in vivo applications.

Ex vivo modification of T lymphocytes, however, has its disadvantages. The complexity of the overall procedure, cost of the manufacturing process, and prolonged ex vivo culture negatively impact the quality of the final product. Methods that improve T lymphocyte engineering that use in vivo delivery platforms are needed.

In vivo delivery platforms using fusogenic glycoproteins of viral vectors have been shown to be beneficial for targeting, binding, and transducing cells of interest. Certain fusogenic glycoproteins, however, may not be sufficiently stable or expressed on the surface of the viral vector. Thus, improved fusogenic glycoproteins, fusosomes and viral vectors containing those glycoproteins are needed. The provided disclosure addresses this need.

The present disclosure provides an antibody or antigen binding fragment thereof that specifically binds CD4, comprising certain heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and/or light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3). Another embodiment is an antibody or antigen binding fragment thereof specifically binding CD4, comprising certain heavy (VH) and/or light (VL) chain variable regions. The disclosure likewise provides for isolated nucleotides, vectors, and host cells comprising the anti-CD4 antibody or antigen binding fragment thereof.

The present disclosure also provides a fusion protein comprising a glycoprotein G (G protein), hemagglutinin (H Protein), or hemagglutinin-neuraminidase (HN Protein), or a biologically active portion thereof of the Paramyxoviridae family and at least one disclosed CD4 antibody or antigen binding fragment, wherein the antibody or antigen binding fragment is fused to the C-terminus of the G protein or the biologically active portion thereof.

The present disclosure also provides a fusosome comprising at least one antibody or antigen binding fragment thereof that specifically binds CD4, and at least one fusogen. The antibody or antigen binding fragment thereof that specifically binds CD4 may be any antibody or antigen binding fragment thereof that specifically binds CD4, including any antibody or antigen binding fragment thereof that specifically binds CD4 described herein. In some embodiments the fusogen and the antibody or antigen binding fragment thereof that specifically binds CD4 are linked within the fusosome, for example via a linker sequence. In some embodiments the fusogen and the antibody or antigen binding fragment thereof that specifically binds CD4 are not linked within the fusosome. In some embodiments the fusogen and the antibody or antigen binding fragment thereof that specifically binds CD4 are operably linked. The fusogen may be any fusogen, including any fusogen described herein. In some embodiments the fusogen is a G protein, including any G protein described herein. The present disclosure also provides a viral vector comprising a F protein molecule or biologically active portion thereof of the Paramyxoviridae family, an envelope glycoprotein G (G protein), hemagglutinin (H Protein), or hemagglutinin-neuraminidase (HN Protein), or a biologically active portion thereof of the Paramyxoviridae family, and at least one disclosed CD4 antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof is attached to the C-terminus of the G protein or the biologically active portion thereof.

The present disclosure likewise relates to methods of selectively modulating and transducing CD4+ T cells using the disclosed fusosomes or viral vectors. Also disclosed are methods of delivering an exogenous agent to a subject, comprising administering to the subject the disclosed fusosomes or viral vectors, in which the fusosomes or viral vector further comprises an exogenous agent. The present disclosure also relates to methods of treating cancer in a subject, comprising administering to the subject the disclosed viral vectors, and corresponding first and second medical uses.

The present disclosure also provides compositions comprising the fusosomes or fusion proteins or viral vectors of the invention, comprising an antibody or antigen binding fragment thereof that specifically binds CD4, for use as a medicament.

The present disclosure also provides compositions comprising the fusosomes or fusion proteins or viral vectors of the invention, comprising an antibody or antigen binding fragment thereof that specifically binds CD4, for use in a method of treating cancer.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows an exemplary system for administration of a lentiviral vector comprising a CD4 binding agent to a subject.

FIG. 2 shows off-target transduction of certain CD4 binders using CD4 knockout SupT1 cells and HEK-293T cells, as assessed by measuring percentage of GFP-expressing cells with flow cytometry.

FIG. 3 shows the flow cytometry data for CD4 retargeted fusogens on PBMCs.

FIG. 4 shows the percent of GFP+ cells of retargeted fusogens in donor PBMCs.

FIG. 5A shows tumor burden at Day 21 in CD19+ tumor bearing mice treated with 2.5E6, 5E6, or 1E7 integrating units (IU) of Binder 256, as assessed by bioluminescence imaging.

FIG. 5B shows tumor burden at Day 21 in CD19+ tumor bearing mice treated with 2.5E6, 5E6, or 1E7 IU of a CD8 Binder Control, as assessed by bioluminescence imaging.

FIG. 5C shows tumor burden at Day 21 in CD19+ tumor bearing mice treated with 2.5E6, 5E6, or 1E7 integrating units IU of Binder 75, as assessed by bioluminescence imaging.

FIG. 5D shows the percentage of CD4+ T cells that express CAR at Day 15 in CD19+ tumor bearing mice treated with 2.5E6, 5E6, or 1E7 integrating units (IU) of CD4-targeted CD19 CAR fusosomes, as assessed by flow cytometry.

DETAILED DESCRIPTION

Unless defined otherwise, all terms of art, notations, and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art, unless such differences are expressly noted.

Unless defined otherwise, all technical and scientific terms, acronyms, and abbreviations used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains. Unless indicated otherwise, abbreviations and symbols for chemical and biochemical names is per IUPAC-IUB nomenclature. Unless indicated otherwise, all numerical ranges are inclusive of the values defining the range as well as all integer values in-between.

As used herein, the articles “a” and “an” refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

As used herein, the term “about” will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which it is used. In some embodiments, the term “about” when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass art-accepted variations based on standard errors in making such measurements. In some embodiments, the term “about” when referring to such values, is meant to encompass variations of ±20% or ±10%, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

As used herein, “CD4” or “cluster of differentiation 4” refers to a transmembrane glycoprotein which is a specific marker for a subclass of T cells (which includes helper T cells). The CD4 protein acts as a co-receptor together with the T cell receptor (TCR) to recognize antigen presentation by MHC class II cells. CD4 plays a role in the development of T cells and activation of mature T cells.

As used herein, “affinity” refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). The affinity of a molecule for its partner can generally be represented by the equilibrium dissociation constant (K_D) (or its inverse equilibrium association constant, KA). Affinity can be measured by common methods known in the art, including those described herein. See, for example, surface plasmon resonance methods described in Pope M. E., Soste M. V., Eyford B. A., Anderson N. L., Pearson T. W., (2009) J. Immunol. Methods. 341(1-2):86-96, and methods described therein.

As used herein, “antibody” is meant in a broad sense and includes immunoglobulin molecules including monoclonal antibodies including murine, human, humanized, and chimeric antibodies, antibody fragments, bispecific or multispecific antibodies formed from at least two intact antibodies or antibody fragments, dimeric, tetrameric or multimeric antibodies, single chain antibodies, and any other modified configuration of the immunoglobulin molecule that comprises an antigen recognition site of the required specificity.

Immunoglobulins can be assigned to five major classes, namely IgA, IgD, IgE, IgG, and IgM, depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub-classified to IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Antibody light chains of any vertebrate species can be assigned to one of two types, namely kappa (κ) and lambda (A), based on the amino acid sequences of their constant domains.

As used herein, “antigen binding fragment” or “antibody fragment” refers to a portion of an immunoglobulin molecule that retains the heavy chain and/or the light chain antigen binding site, such as the heavy chain complementarity determining regions (HCDR) 1 (HCDR1), 2 (HCDR2), and 3 (HCDR3), the light chain complementarity determining regions (LCDR) 1 (LCDR1), 2 (LCDR2), and 3 (LCDR3), the heavy chain variable region (VH), or the light chain variable region (VL). Antibody fragments include a Fab fragment (a monovalent fragment comprising the VL or the VH); a F (ab) 2 fragment (a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region); a Fd fragment comprising the VH and CH1 domains; a Fv fragment comprising the VL and VH domains of a single arm of an antibody; a dAb fragment, which comprises a VH domain; and a variable domain (e.g., VNAR, VHH, etc.) from, e.g., human, shark, or camelid origin. VH and VL domains can be engineered and linked together via one or more synthetic linkers to form various types of single chain antibody designs in which the VH/VL domains pair intramolecularly, or intermolecularly in those cases in which the VH and VL domains are expressed by separate single chain antibody constructs, to form a monovalent antigen binding site, such as a single-chain Fv (scFv) or diabody. Such antibody fragments may be obtained using well known techniques and the fragments may be characterized in the same manner as are intact antibodies.

An antibody variable region comprises a “framework” region interrupted by three “antigen binding sites.” The antigen binding sites are defined using various terms, including, for example (i) “Complementarity Determining Regions” (CDRs), three in the VH (HCDR1, HCDR2, HCDR3) and three in the VL (LCDR1, LCDR2, LCDR3) (Wu and Kabat, J Exp Med 132:211-50, 1970; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), and (ii) “Hypervariable regions,” “HVR,” or “HV,” three in the VH (H1, H2, H3) and three in the VL (L1, L2, L3) (Chothia and Lesk Mol Biol 196:901-17, 1987). Other terms include “IMGT-CDRs” (Lefranc et al., Dev Comparat Immunol 27:55-77, 2003) and “Specificity Determining Residue Usage” (SDRU) (Almagro Mol Recognit, 17:132-43, 2004). The International ImMunoGeneTics (IMGT) database (http://www_imgt org) provides a standardized numbering and definition of antigen-binding sites. The correspondence between CDRs, HVs, and IMGT delineations is described in Lefranc et al., Dev Comparat Immunol 27:55-77, 2003.

The term “framework,” or “FR” or “framework sequence” refers to the remaining sequences of a variable region other than those sequences defined to be antigen binding sites. Because the antigen binding site can be defined by various terms as described above, the exact amino acid sequence of a framework depends on how the antigen-binding site was defined.

The term “CDR” denotes a complementarity determining region as defined by at least one manner of identification to one of skill in the art. The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme); Al-Lazikani et al., (1997) JMB 273,927-948 (“Chothia” numbering scheme); MacCallum et al., J. Mol. Biol. 262:732-745 (1996), “Antibody-antigen interactions: Contact analysis and binding site topography,” J. Mol. Biol. 262, 732-745.” (“Contact” numbering scheme); Lefranc M P et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol, 2003 January; 27(1):55-77 (“IMGT” numbering scheme); Honegger A and Plückthun A, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J Mol Biol, 2001 Jun. 8; 309(3):657-70, (“Aho” numbering scheme); and Martin et al., “Modeling antibody hypervariable loops: a combined algorithm,” PNAS, 1989, 86(23):9268-9272, (“AbM” numbering scheme).

The boundaries of a given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignments, while the Chothia scheme is based on structural information. Numbering for both the Kabat and Chothia schemes is based upon the most common antibody region sequence lengths, with insertions accommodated by insertion letters, for example, “30a,” and deletions appearing in some antibodies. The two schemes place certain insertions and deletions (“indels”) at different positions, resulting in differential numbering. The Contact scheme is based on analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme. The AbM scheme is a compromise between the Kabat and Chothia definitions based on that used by Oxford Molecular's AbM antibody modeling software.

In some embodiments, CDRs are defined in accordance with any of the Chothia numbering schemes, the Kabat numbering scheme, the IMGT numbering scheme, a combination of Kabat, IMGT, and Chothia, the AbM definition, and/or the contact definition. A sdAb variable domain comprises three CDRs, designated CDR1, CDR2, and CDR3. Table 1, below, lists exemplary position boundaries of CDR-H1, CDR-H2, CDR-H3 as identified by Kabat, Chothia, AbM, and Contact schemes, respectively. For CDR-H1, residue numbering is listed using both the Kabat and Chothia numbering schemes. FRs are located between CDRs, for example, with FR-H1 located before CDR-H1, FR-H2 located between CDR-H1 and CDR-H2, FR-H3 located between CDR-H2 and CDR-H3 and so forth. It is noted that because the shown Kabat numbering scheme places insertions at H35A and H35B, the end of the Chothia CDR-H1 loop when numbered using the shown Kabat numbering convention varies between H32 and H34, depending on the length of the loop.

TABLE 1
Boundaries of CDRs according to various numbering schemes.

CDR	Kabat	Chothia	AbM	Contact
CDR-H1	H31--H35B	H26--H32 . . .	H26--H35B	H30--H35B
(Kabat		34
Numbering1)
CDR-H1	H31--H35	H26--H32	H26--H35	H30--H35
(Chothia
Numbering2)
CDR-H2	H50--H65	H52--H56	H50--H58	H47--H58
CDR-H3	H95--H102	H95--H102	H95--H102	H93--H101
1Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD
2Al-Lazikani et al., (1997) JMB 273,927-948.

Thus, unless otherwise specified, a “CDR” or “complementary determining region,” or individual specified CDRs (e.g., CDR-H1, CDR-H2, CDR-H3), of a given antibody or region thereof, such as a variable region thereof, should be understood to encompass a (or the specific) complementary determining region as defined by any of the aforementioned schemes. For example, where it is stated that a particular CDR (e.g., a CDR-H3) contains the amino acid sequence of a corresponding CDR in a given sdAb amino acid sequence, it is understood that such a CDR has a sequence of the corresponding CDR (e.g., CDR-H3) within the sdAb, as defined by any of the aforementioned schemes. It is understood that any antibody, such as a sdAb, includes CDRs and such can be identified according to any of the other aforementioned numbering schemes or other numbering schemes known to a skilled artisan.

As used herein, “Fv” refers to the minimum antibody fragment which contains a complete antigen-recognition and antigen-binding site. This region comprises a dimer of one heavy chain and one light chain variable domain in tight, non-covalent association. It is in this configuration that the three hypervariable regions of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six hypervariable regions confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three hypervariable regions specific for an antigen) may have the ability to recognize and bind an antigen, although at a lower affinity than the entire binding site.

As used herein, “single-chain Fv” or “scFv” antibody fragments comprise the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. Preferably, the Fv polypeptide further comprises a linker (e.g., a polypeptide linker) between the VH and VL domains which enables the scFv to form the desired structure for antigen binding. For a review of scFv see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

As used herein, “VHH” or “VHH antibodies” refer to single domain antibodies that comprise the variable (antigen binding) domain of the heavy chain antibody (HCAb or hcIgG) molecules produced by Camelidae family mammals (e.g., llamas, camels, and alpacas).

As used herein, “VNAR” or “VNAR antibodies” refer to single domain antibodies that comprise the variable (antibody binding) domain of the shark immunoglobulin new antigen receptors (IgNARs).

As used herein, the term “specifically binds” to a target molecule, such as an antigen, means that a binding molecule, such as a single domain antibody, reacts or associates more frequently, more rapidly, with greater duration, and/or with greater affinity with a particular target molecule than it does with alternative molecules. A binding molecule, such as a sdAb or scFv, “specifically binds” to a target molecule if it binds with greater affinity, avidity, more readily, and/or with greater duration than it binds to other molecules. It is understood that a binding molecule, such as a sdAb or scFv, that specifically binds to a first target may or may not specifically bind to a second target. As such, “specific binding” does not necessarily require (although it can include) exclusive binding.

As used herein, “percent (%) sequence identity” with respect to an amino acid or nucleic acid sequence is defined as the percentage of amino acid or nucleic acid residues in a candidate sequence that are identical with the amino acid or nucleic acid residues in another amino acid or nucleic acid sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Percent identity between nucleic acid sequences may be determined using a suite of commonly used and freely available sequence comparison algorithms provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, Md., and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

An amino acid substitution may include but is not limited to the replacement of one amino acid in a polypeptide with another amino acid. Exemplary substitutions are shown in Table 2. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, for example, retained/improved binding.

	TABLE 2
	Original Residue	Exemplary Substitutions
	Ala (A)	Val; Leu; Ile
	Arg (R)	Lys; Gln; Asn
	Asn (N)	Gln; His; Asp, Lys; Arg
	Asp (D)	Glu; Asn
	Cys (C)	Ser; Ala
	Gln (Q)	Asn; Glu
	Glu (E)	Asp; Gln
	Gly (G)	Ala
	His (H)	Asn; Gln; Lys; Arg
	Ile (I)	Leu; Val; Met; Ala; Phe; Norleucine
	Leu (L)	Norleucine; Ile; Val; Met; Ala; Phe
	Lys (K)	Arg; Gln; Asn
	Met (M)	Leu; Phe; Ile
	Phe (F)	Trp; Leu; Val; Ile; Ala; Tyr
	Pro (P)	Ala
	Ser (S)	Thr
	Thr (T)	Val; Ser
	Trp (W)	Tyr; Phe
	Tyr (Y)	Trp; Phe; Thr; Ser
	Val (V)	Ile; Leu; Met; Phe; Ala; Norleucine

Amino acids may be grouped according to common side-chain properties:

• • (1) hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile;
  • (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;
  • (3) acidic: Asp, Glu;
  • (4) basic: His, Lys, Arg;
  • (5) residues that influence chain orientation: Gly, Pro;
  • (6) aromatic: Trp, Tyr, Phe.

Non-conservative substitutions will entail exchanging a member of one of these classes for another class. The term, “corresponding to” with reference to nucleotide or amino acid positions of a sequence, such as set forth in the Sequence Listing, refers to nucleotide or amino acid positions identified upon alignment with a target sequence based on structural sequence alignment or using a standard alignment algorithm, such as the GAP algorithm. For example, corresponding residues of a similar sequence (e.g. fragment or species variant) can be determined by alignment to a reference sequence by structural alignment methods. By aligning the sequences, one skilled in the art can identify corresponding residues, for example, using conserved and identical amino acid residues as guides.

The term “isolated” as used herein refers to a molecule that has been separated from at least some of the components with which it is typically found in nature or produced. For example, a polypeptide is referred to as “isolated” when it is separated from at least some of the components of the cell in which it was produced. When a polypeptide is secreted by a cell after expression, physically separating the supernatant containing the polypeptide from the cell that produced it is considered to be “isolating” the polypeptide. Similarly, a polynucleotide is referred to as “isolated” when it is not part of the larger polynucleotide (such as, for example, genomic DNA or mitochondrial DNA, in the case of a DNA polynucleotide) in which it is typically found in nature, or is separated from at least some of the components of the cell in which it was produced. Thus, a DNA polynucleotide that is contained in a vector inside a host cell may be referred to as “isolated.”

As used herein, “lipid particle” refers to any biological or synthetic particle that contains a bilayer of amphipathic lipids enclosing a lumen or cavity. Typically, a lipid particle does not contain a nucleus. Examples of lipid particles include nanoparticles, viral-derived particles, or cell-derived particles. Such lipid particles include, but are not limited to, viral particles (e.g. lentiviral particles), virus-like particles, viral vectors (e.g., lentiviral vectors), exosomes, enucleated cells, vesicles (e.g., microvesicles, membrane vesicles, extracellular membrane vesicles, plasma membrane vesicles, and giant plasma membrane vesicles), apoptotic bodies, mitoparticles, pyrenocytes, or lysosomes. In some embodiments, a lipid particle is a fusosome. In some embodiments, the lipid particle is not a platelet.

As used herein a “biologically active portion,” such as with reference to a protein such as a G protein or an F protein, refers to a portion of the protein that exhibits or retains an activity or property of the full-length of the protein. For example, a biologically active portion of an F protein retains fusogenic activity in conjunction with the G protein when each are embedded in a lipid bilayer. A biologically active portion of the G protein retains fusogenic activity in conjunction with an F protein when each is embedded in a lipid bilayer. The retained activity can include 10%-150% or more of the activity of a full-length or wild-type F protein or G protein. Examples of biologically active portions of F and G proteins include truncations of the cytoplasmic domain, e.g. truncations of up to 1, 2, 3, 4, 5, 6, 7, 8 9, 10, 11, 12, 13, 14, 15, 20, 22, 25, 30, 33, 34, 35, or more contiguous amino acids, see e.g. Khetawat and Broder 2010 Virology Journal 7:312; Witting et al. 2013 Gene Therapy 20:997-1005; published international; patent application No. WO/2013/148327.

As used herein, “G protein” refers to an envelope attachment glycoprotein G or biologically active portion thereof of the Paramyxoviridae family. “F protein” refers to a fusion protein F or biologically active portion thereof of the Paramyxoviridae family. “H protein” refers to an envelope attachment protein with haemagglutination activity. Morbilliviruses attachment proteins are designated H proteins. “HN protein” refers to an envelope attachment protein with haemagglutination-neuraminidase activity. Respiroviruses, rubulaviruses and avulaviruses attachment proteins are designated HN proteins. H, HN, and G proteins are cell attachment proteins that span the viral envelope and project from the surface as spikes. These proteins bind to proteins on the surface of target cells to facilitate cell entry.

The F and G proteins may be from a henipavirus, a Hendra (HeV) virus, or a Nipah (NiV) virus, and may be a wild-type protein or may be a variant thereof that exhibits reduced binding for the native binding partner. The F (fusion) and G (attachment) glycoproteins mediate cellular entry of Nipah virus. The G protein initiates infection by binding to the cellular surface receptor ephrin-B2 (EphB2) or EphB3. The subsequent release of the viral genome into the cytoplasm is mediated by the action of the F protein, which induces the fusion of the viral envelope with cellular membranes. The efficiency of transduction of targeted lipid particles can be improved by engineering hyperfusogenic mutations in one or both of the F protein (such as NiV-F) and G protein (such as NiV-G).

As used herein, “fusosome” refers to a particle containing a bilayer of amphipathic lipids enclosing a lumen or cavity and a fusogen that interacts with the amphipathic lipid bilayer. In some embodiments, the fusosome comprises a nucleic acid. In some embodiments, the fusosome is a membrane enclosed preparation. In some embodiments, the fusosome is derived from a source cell. In some embodiments the fusosme is a vector. In some embodiments the fusosome is an integrating vector. In some embodiments the fusosome is a viral vector. In some embodiments the fusosome is a lipid particle, including a targeted lipid particle, including any lipid particle or targeted lipid particle described herein. As used herein, “fusosome composition” refers to a composition comprising one or more fusosomes.

As used herein, “fusogen” refers to an agent or molecule that creates an interaction between two membrane enclosed lumens. In embodiments, the fusogen facilitates fusion of the membranes. In other embodiments, the fusogen creates a connection, e.g., a pore, between two lumens (e.g., a lumen of a retroviral vector and a cytoplasm of a target cell). In some embodiments, the fusogen comprises a complex of two or more proteins, e.g., wherein neither protein has fusogenic activity alone. In some embodiments, the fusogen comprises a targeting domain.

As used herein, a “re-targeted fusogen” refers to a fusogen that comprises a targeting moiety having a sequence that is not part of the naturally-occurring form of the fusogen. In embodiments, the fusogen comprises a different targeting moiety relative to the targeting moiety in the naturally-occurring form of the fusogen. In embodiments, the naturally-occurring form of the fusogen lacks a targeting domain, and the re-targeted fusogen comprises a targeting moiety that is absent from the naturally-occurring form of the fusogen. In embodiments, the fusogen is modified to comprise a targeting moiety. In embodiments, the fusogen comprises one or more sequence alterations outside of the targeting moiety relative to the naturally-occurring form of the fusogen, e.g., in a transmembrane domain, fusogenically active domain, or cytoplasmic domain.

As used herein, a “targeted envelope protein” refers to a polypeptide that contains a G protein (G protein), hemagglutinin (H Protein), or hemagglutinin-neuraminidase (HN Protein), of the Paramyxoviridae family attached to a single domain antibody (sdAb) variable domain, such as a VL or VH sdAb, a scFv, a nanobody, a camelid VHH domain, a shark VNAR, or fragments thereof, that target a molecule on a desired cell type. In some such embodiments, the attachment may be direct or indirect via a linker, such as a polypeptide linker. The “targeted envelope protein” may also be referred to as a “fusion protein” comprising the G protein and antibodies or antigen binding fragments of the disclosure in which the antibody or antigen binding fragment is fused to the C-terminus of the G protein or a biologically active portion thereof.

As used herein, a “targeted lipid particle” refers to a lipid particle that contains a targeted envelope protein embedded in the lipid bilayer, e.g., targeting CD4. Such targeted lipid particles can be a viral particle, a virus-like particle, a nanoparticle, a vesicle, an exosome, a dendrimer, a lentivirus, a viral vector, an enucleated cell, a microvesicle, a membrane vesicle, an extracellular membrane vesicle, a plasma membrane vesicle, a giant plasma membrane vesicle, an apoptotic body, a mitoparticle, a pyrenocyte, a lysosome, another membrane enclosed vesicle, a lentiviral vector, a viral based particle, a virus like particle (VLP), or a cell derived particle.

As used herein, a “retroviral nucleic acid” refers to a nucleic acid containing at least the minimal sequence requirements for packaging into a retrovirus or retroviral vector, alone or in combination with a helper cell, helper virus, or helper plasmid. In some embodiments, the retroviral nucleic acid further comprises or encodes an exogenous agent, a positive target cell-specific regulatory element, a non-target cell-specific regulatory element (TCSRE), or a negative TCSRE. In some embodiments, the retroviral nucleic acid comprises one or more of (e.g., all of) a 5′ LTR (e.g., to promote integration), U3 (e.g., to activate viral genomic RNA transcription), R (e.g., a Tat-binding region), U5, a 3′ LTR (e.g., to promote integration), a packaging site (e.g., psi (′)), and RRE (e.g., to bind to Rev and promote nuclear export). The retroviral nucleic acid can comprise RNA (e.g., when part of a virion) or DNA (e.g., when being introduced into a source cell or after reverse transcription in a recipient cell). In some embodiments, the retroviral nucleic acid is packaged using a helper cell, helper virus, or helper plasmid which comprises one or more of (e.g., all of) gag, pol, and env.

As used herein, a “target cell” refers to a cell of a type to which it is desired that a targeted lipid particle delivers an exogenous agent. In embodiments, a target cell is a cell of a specific tissue type or class, e.g., an immune effector cell, e.g., a T cell. In some embodiments, a target cell is a diseased cell, e.g., a cancer cell. In some embodiments, the fusogen, e.g., a re-targeted fusogen, leads to preferential delivery of the exogenous agent to a target cell compared to a non-target cell.

As used herein a “non-target cell” refers to a cell of a type to which it is not desired that a targeted lipid particle delivers an exogenous agent. In some embodiments, a non-target cell is a cell of a specific tissue type or class. In some embodiments, a non-target cell is a non-diseased cell, e.g., a non-cancerous cell. In some embodiments, the fusogen, e.g., a re-targeted fusogen, leads to lower delivery of the exogenous agent to a non-target cell compared to a target cell.

The term “effective amount” as used herein means an amount of a pharmaceutical composition which is sufficient to significantly and positively modify the symptoms and/or conditions to be treated (e.g., provide a positive clinical response). The effective amount of the targeted lipid particles of the disclosure for use in a pharmaceutical composition will vary with the particular condition being treated, the severity of the condition, the duration of treatment, the nature of concurrent therapy, the particular lipid particle being employed, the particular pharmaceutically-acceptable excipient(s) and/or carrier(s) utilized, and like factors within the knowledge and expertise of the attending physician.

An “exogenous agent” as used herein with reference to a targeted lipid particle, refers to an agent that is neither comprised by nor encoded in the corresponding wild-type virus or fusogen made from a corresponding wild-type source cell. In some embodiments, the exogenous agent does not naturally exist, such as a protein or nucleic acid that has a sequence that is altered (e.g., by insertion, deletion, or substitution) relative to a naturally occurring protein. In some embodiments, the exogenous agent does not naturally exist in the source cell. In some embodiments, the exogenous agent exists naturally in the source cell but is exogenous to the virus. In some embodiments, the exogenous agent does not naturally exist in the recipient cell. In some embodiments, the exogenous agent exists naturally in the recipient cell, but is not present at a desired level or at a desired time. In some embodiments, the exogenous agent comprises DNA, RNA, or protein.

As used herein, a “promoter” refers to a cis-regulatory DNA sequence that, when operably linked to a gene coding sequence, drives transcription of the gene. The promoter may comprise one or more transcription factor binding sites. In some embodiments, a promoter works in concert with one or more enhancers which are distal to the gene.

As used herein, “operably linked” refers to a polynucleotide sequence that is joined to a regulatory region sequence in a manner that allows expression of the polynucleotide sequence. A regulatory region sequence directs transcription of a polynucleotide sequence, and can include enhancer sequences, response elements, protein recognition sites, inducible elements, promoter control elements, 5′ and 3′ untranslated regions protein binding sequences, transcriptional start sites, termination sequences, polyadenylation sequences, and introns.

As used herein, a composition refers to any mixture of two or more products, substances, or compounds, including cells. It may be a solution, a suspension, a liquid, a powder, a paste, aqueous, non-aqueous, or any combination thereof.

As used herein, the term “pharmaceutically acceptable” refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of a therapeutic compound, and is relatively nontoxic, i.e., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained.

As used herein, the term “pharmaceutical composition” refers to a mixture of at least one targeted lipid particle of the disclosure with other chemical components, such as carriers, stabilizers, diluents, dispersing agents, suspending agents, thickening agents, and/or excipients. The pharmaceutical composition facilitates administration of the targeted lipid particle to an organism. Multiple techniques of administering targeted lipid particles of the disclosure exist in the art including, but not limited to, intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary, and topical administration.

A “disease” or “disorder” as used herein refers to a condition for which treatment is needed and/or desired.

As used herein, the terms “treat,” “treating,” or “treatment” refer to ameliorating a disease or disorder, e.g., slowing or arresting or reducing the development of the disease or disorder or reducing at least one of the clinical symptoms thereof. For purposes of this disclosure, ameliorating a disease or disorder can include obtaining a beneficial or desired clinical result that includes, but is not limited to, any one or more of: alleviation of one or more symptoms, diminishment of extent of disease, preventing or delaying spread (for example, metastasis, for example metastasis to the lung or to the lymph node) of disease, preventing or delaying recurrence of disease, delay or slowing of disease progression, amelioration of the disease state, inhibiting the disease or progression of the disease, inhibiting or slowing the disease or its progression, arresting its development, and remission (whether partial or total).

The terms “individual” and “subject” are used interchangeably herein to refer to an animal; for example a mammal. The terms include human and veterinary animals. In some embodiments, methods of treating animals, including, but not limited to, humans, rodents, simians, felines, canines, equines, bovines, porcines, ovines, caprines, mammalian laboratory animals, mammalian farm animals, mammalian sport animals, and mammalian pets, are provided. The animal can be male or female and can be any suitable age, including infant, juvenile, adolescent, adult, and geriatric. In some examples, an “individual” or “subject” refers to an animal in need of treatment for a disease or disorder. In some embodiments, the animal to receive the treatment is a “patient,” designating the fact that the animal has been identified as having a disorder of relevance to the treatment, or being at adequate risk of contracting the disorder. In particular embodiments, the animal is a human, such as a human patient.

CD4-Specific Antibodies

Described herein are novel antibodies and antigen binding fragments thereof that specifically target and bind CD4. In some embodiments, the antibodies or antigen binding fragments thereof cross-react with cynomolgus (or “cyno”) or M. nemestrina CD4. In some embodiments, the antibodies or antigen binding fragments thereof are single-chain variable fragments (scFvs) composed of the antigen-binding domains derived from the heavy (VH) and the light (VL) chains of an IgG molecule and connected via a linker domain. In some embodiments, the antibodies or antigen binding fragments thereof are VHHs or VNARs that correspond to the antigen binding domains of the camelid and shark IgG molecules, respectively. The present disclosure also provides polynucleotides encoding the antibodies and fragments thereof, vectors, and host cells, and methods of using the antibodies or antigen binding fragments thereof. In some embodiments, e.g., the antibodies or antigen binding fragments thereof fuse to a glycoprotein (G Protein), hemagglutinin (H Protein), or hemagglutinin-neuraminidase (HN Protein) of the Paramyxoviridae family for targeted binding and transduction to cells.

Sequences for exemplary antibodies and antigen binding fragments of the disclosure using the Kabat numbering scheme are shown in Tables 19-22 below. Sequences for exemplary HCDRs and LCDRs of the disclosure are shown in Table 22.

The sequences for the disclosed VH and VL domains are provided in Tables 20-21. Tables 23-24 provided herein show the CDR sequences of the disclosed antibodies and antigen binding fragments thereof using both Chothia and IMGT numbering schemes, respectively. The full CD4 binder sequences of the variant CD4 scFvs and VHHs of the disclosure are shown in Table 19.

In some embodiments, an antibody or antigen binding fragment thereof capable of binding CD4 is disclosed, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3). In some embodiments, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise amino acid sequences of any one of the SEQ ID NOs recited in Table 22. In some embodiments, the heavy chain variable region (VH) comprises an amino acid sequence of any one of SEQ ID NOs: 256-511, 9447-9576, or 14000-14002 (Table 20) and the light chain variable region (VL) comprises an amino acid sequence of any one of SEQ ID NOs: 512-766 or 9577-9706 (Table 21).

In another embodiment, the antibody or antigen binding fragment thereof comprises a VH having an amino acid sequence with at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 256-511, 9447-9576, or 14000-14002.

In another embodiment, the antibody or antigen binding fragment thereof comprises a VL having an amino acid sequence with at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 512-766 or 9577-9706.

In another embodiment, the antibody or antigen binding fragment comprises a VH having an amino acid sequence with at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 256-511, 9447-9576, or 14000-14002 and a VL having an amino acid sequence with at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 512-766 or 9577-9706.

In another embodiment, the antibody or antigen binding fragment thereof comprises a VH having an amino acid sequence with at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 256.

In another embodiment, the antibody or antigen binding fragment thereof comprises the VH of SEQ ID NO: 304 and the VL of SEQ ID NO: 559.

In another embodiment, the antibody or antigen binding fragment thereof comprises the VH of SEQ ID NO: 331 and the VL of SEQ ID NO: 586.

In another embodiment, the antibody or antigen binding fragment thereof comprises the VH of SEQ ID NO: 9554 and the VL of SEQ ID NO: 9684.

In another embodiment, the antibody or antigen binding fragment thereof comprises the VH of SEQ ID NO: 256.

In another embodiment, the antibody or antigen binding fragment thereof comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of SEQ ID NOs: 1308, 1822, 2336, 5672, 6182, 6692, respectively.

In another embodiment, the antibody or antigen binding fragment thereof comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of SEQ ID NOs: 1376, 1890, 2404, 5740, 6250, 6760, respectively.

In another embodiment, the antibody or antigen binding fragment thereof comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of SEQ ID NOs: 10074, 10336, 10598, 12300, 12560, 12820, respectively.

In another embodiment, the antibody or antigen binding fragment thereof comprises the HCDR1, HCDR2, and HCDR3 of SEQ ID NOs: 1535, 2049, 2563, respectively.

In some embodiments, the single domain antibody is human or humanized. In some embodiments, the single domain antibody or portion thereof is naturally occurring. In some embodiments, the single domain antibody or portion thereof is synthetic.

In some embodiments, the single domain antibodies are antibodies whose complementary determining regions are part of a single domain polypeptide. In some embodiments, the single domain antibody is a heavy chain only antibody variable domain. In some embodiments, the single domain antibody does not include light chains.

In various embodiments, any of the antibodies or antigen binding fragments described herein comprise a heavy chain constant region and a light chain constant region. The heavy chain constant region may be an IgG, IgM, IgA, IgD, or IgE isotype, or a derivative or fragment thereof that retains at least one effector function of the intact heavy chain. The heavy chain constant region may be a human IgG isotype. The heavy chain constant region may be a human IgG1 or human IgG4 isotypes. The heavy chain constant region may be a human IgG1 isotype. The light chain constant region may be a human kappa light chain or lambda light chain or a derivative or fragment thereof that retains at least one effector function of the intact light chain. The light chain constant region may be a human kappa light chain.

In various embodiments, any of the disclosed antibodies or antigen binding fragments may be a rodent antibody or antigen binding fragment thereof, a chimeric antibody or an antigen binding fragment thereof, a CDR-grafted antibody or an antigen binding fragment thereof, or a humanized antibody or an antigen binding fragment thereof. In another embodiment, any of the disclosed antibodies or antigen binding fragments comprises human or human-derived heavy and light chain variable regions, including human frameworks or human frameworks with one or more backmutations. In various embodiments, any of the disclosed antibodies or antigen binding fragments may be a Fab, Fab′, F(ab′)2, Fd, scFv, (scFv)2, scFv-Fc, VHH, or Fv fragment.

Antibodies whose heavy chain CDR, light chain CDR, VH, or VL amino acid sequences differ insubstantially from those shown in Tables 19-24 are encompassed within the scope of the disclosure. Typically, this involves one or more conservative amino acid substitutions with an amino acid having similar charge, hydrophobic, or stereo chemical characteristics in the antigen-binding site or in the framework without adversely altering the properties of the antibody. Conservative substitutions may also be made to improve antibody properties, for example stability or affinity. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid substitutions can be made to the VH or VL sequence. For example, a “conservative amino acid substitution” may involve a substitution of a native amino acid residue with a nonnative residue such that there is little or no effect on the polarity or charge of the amino acid residue at that position. Desired amino acid substitutions can be determined by those skilled in the art at the time such substitutions are desired. For example, amino acid substitutions can be used to identify important residues of the molecule sequence, or to increase or decrease the affinity of the molecules described herein. The following eight groups contain amino acids that are conservative amino acid substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine(S), Threonine (T); and 8) Cysteine (C), Methionine (M).

In some embodiments, the antibody or antigen binding fragment binding CD4 is a single-chain variable fragment. In embodiments involving a single polypeptide containing both a heavy chain variable region and a light chain variable region, both orientations of these variable regions are contemplated. In some cases, the heavy chain variable region is on the N-terminal side of the light chain variable region, which means the heavy chain variable region is closer to the N-terminus of the polypeptide. In other cases, the light chain variable region is on the N-terminal side of the heavy chain variable region, which means the light chain variable region is closer to the N-terminus of the polypeptide than the heavy chain variable region.

In some embodiments, the scFv binding proteins comprise a linker. In some embodiments, the linker is between the heavy chain variable region (VH) and the light chain variable region (VL) (or vice versa). In some embodiments, the linker comprises the amino acid sequence of GS, GGS, GGGS (SEQ ID NO: 14125), GGGGS (SEQ ID NO: 9294), GGGGGS (SEQ ID NO: 9292), any one of SEQ ID NOs: 9312-9315, or combinations thereof. Substitutions to introduce new disulfide bonds are also within the scope of the disclosure, e.g., by making substitutions G44C in the VH FR 2 and G100C in the VL FR4.

In some embodiments, the anti-CD4 antibody or antigen binding fragment binds to human CD4 with an affinity constant (K_D) of about 1 nM to about 900 nM. In some embodiments, the K_D to human CD4 is about 5 nM to about 500 nM, about 6 nM to about 10 nM, about 11 nM to about 20 nM, about 25 nM to about 40 nM, about 40 nM to about 60 nM, about 70 nM to about 90 nM, about 100 nM to about 120 nM, about 125 nM to about 140 nM, about 145 nM to about 160 nM, about 170 nM and to about 200 nM, about 210 nM to about 250 nM, about 260 nM to about 300 nM, about 310 nM to about 350 nM, about 360 nM to about 400 nM, about 410 nM to about 450 nM, and about 460 nM to about 500 nM. In some embodiments, the anti-CD4 antibody or antigen binding fragment binds to human CD4 with an affinity constant (K_D) of 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 50 nM, 20 nM, or 10 nM or lower. In some embodiments, the anti-CD4 antibody or antigen binding fragment binds to human CD4 and CD4 of a non-human primate including cynomolgus, M. mulatta (rhesus monkey), or M. nemestrina CD4 with comparable binding affinity (K_D).

In some embodiments, the anti-CD4 antibody or antigen binding fragment binds to a non-human primate, cynomolgus, M. mulatta (rhesus monkey), or N. nemestrina CD4. In some embodiments, the anti-CD4 antibody or antigen binding binds to mouse, dog, pig, etc., CD4. In some embodiments, the K_D to a non-human primate, cynomolgus or M. nemestrina CD4 is about 5 nM to about 500 nM, about 6 nM to about 10 nM, about 11 nM to about 20 nM, about 25 nM to about 40 nM, about 40 nM to about 60 nM, about 70 nM to about 90 nM, about 100 nM to about 120 nM, about 125 nM to about 140 nM, about 145 nM to about 160 nM, about 170 nM and to about 200 nM, about 210 nM to about 250 nM, about 260 nM to about 300 nM, about 310 nM to about 350 nM, about 360 nM to about 400 nM, about 410 nM to about 450 nM, and about 460 nM to about 500 nM. In some embodiments, the anti-CD4 antibody or antigen binding fragment binds to cynomolgus or M. nemestrina CD4 with an affinity constant (K_D) of 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 50 nM, 20 nM, or 10 nM or lower.

An antibody or antigen binding fragment thereof that specifically binds CD4 refers to an antibody or binding fragment that preferentially binds to CD4, respectively, over other antigen targets. As used herein, references to an antibody that “specifically binds CD4” are interchangeable with an “anti-CD4” antibody or an “antibody that binds CD4.” In some embodiments, the antibody or binding fragment capable of binding to CD4 does so with higher affinity for that antigen than others. In some embodiments, the antibody or binding fragment capable of binding CD4 binds to that antigen with a K_D of at least about 10-1, 10-2, 10-3, 10-4, 10-5, 10-6, 10-7, 10-8, 10-9, 10-10, 10-11, 10-12 or greater (or any value in between), e.g., as measured by surface plasmon resonance or other methods known to those skilled in the art.

Another embodiment of the disclosure is an isolated polynucleotide encoding any of the antibody heavy chain variable regions or the antibody light chain variable regions of the disclosure. Certain exemplary polynucleotides are disclosed herein, however, other polynucleotides which, given the degeneracy of the genetic code or codon preferences in a given expression system, encode the antibodies or antigen binding fragments thereof of the disclosure are also within the scope of the disclosure. The polynucleotide sequences encoding a VH or a VL or a fragment thereof of the antibody or antigen binding fragments thereof of the disclosure can be operably linked to one or more regulatory elements, such as a promoter and enhancer, that allow expression of the nucleotide sequence in the intended host cell. The polynucleotide may be a cDNA.

Another embodiment of the disclosure is a vector comprising the polynucleotide of the disclosure. Such vectors may be plasmid vectors, viral vectors, vectors for baculovirus expression, transposon-based vectors, or any other vector suitable for introduction of the polynucleotide of the disclosure into a given organism or genetic background by any means. For example, polynucleotides encoding light and heavy chain variable regions of the antibodies of the disclosure, optionally linked to constant regions, may be inserted into expression vectors. The light and heavy chains can be cloned in the same or different expression vectors. The DNA segments encoding immunoglobulin chains may be operably linked to control sequences in the expression vector(s) that ensure the expression of immunoglobulin polypeptides. Such control sequences include signal sequences, promoters (e.g., naturally associated or heterologous promoters), enhancer elements, and transcription termination sequences, and are chosen to be compatible with the host cell chosen to express the antibody. Once the vector has been incorporated into the appropriate host, the host is maintained under conditions suitable for high level expression of the proteins encoded by the incorporated polynucleotides.

Suitable expression vectors are typically replicable in the host organisms either as episomes or as an integral part of the host chromosomal DNA. Commonly, expression vectors contain selection markers such as ampicillin-resistance, hygromycin-resistance, tetracycline resistance, kanamycin resistance, or neomycin resistance to permit detection of those cells transformed with the desired DNA sequences. Suitable vectors, promoter, and enhancer elements are known in the art; many are commercially available for generating subject recombinant constructs.

Another embodiment of the disclosure is a host cell comprising the vector of the disclosure. The term “host cell” refers to a cell into which a vector has been introduced. It is understood that the term host cell is intended to refer not only to the particular subject cell but to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not be identical to the parent cell, but are still included within the scope of the term “host cell” as used herein. Such host cells may be eukaryotic cells, prokaryotic cells, plant cells, or archaeal cells. Escherichia coli, bacilli, such as Bacillus subtilis, and other Enterobacteriaceae, such as Salmonella, Serratia, and various Pseudomonas species are examples of prokaryotic host cells. Other microbes, such as yeast, are also useful for expression. Saccharomyces (e.g., S. cerevisiae) and Pichia are examples of suitable yeast host cells. Exemplary eukaryotic cells may be of mammalian, insect, avian, or other animal origins.

Fusion Proteins Targeting CD4

Also provided herein are fusion proteins targeting CD4 that may be exposed on the surface on a lipid particle or viral vector. In some embodiments the fusion protein comprises an envelope glycoprotein G, H, and/or an F protein of the Paramyxoviridae family. In some embodiments, the fusion protein contains a henipavirus envelope attachment glycoprotein G (G protein) or a biologically active portion thereof and a single domain antibody (sdAb) variable domain or a single chain variable fragment (scFv). The sdAb variable domain or scFv can be linked directly or indirectly to the G protein. In particular embodiments, the sdAb variable domain or scFv is linked to the C-terminus (C-terminal amino acid) of the G protein or the biologically active portion thereof. The linkage can be via a peptide linker, such as a flexible peptide linker. Table 25 provides a list of non-limiting examples of G proteins. Exemplary full length fusion protein sequences of the disclosure are disclosed in Table 19.

In some embodiments, the G protein is of the Paramyxoviridae family. In some embodiments the G protein is a Henipavirus G protein or a biologically active portion thereof. In some embodiments, the Henipavirus G protein is a Hendra (HeV) virus G protein, a Nipah (NiV) virus G-protein (NIV-G), a Cedar (CedPV) virus G-protein, a Mojiang virus G-protein, a bat Paramyxovirus G-protein, or a biologically active portion thereof. In some embodiments, the fusion protein is glycoprotein GP64 of baculovirus, or glycoprotein GP64 variant E45K/T259A. Non-limiting examples of G proteins include those disclosed in Table 25.

In some embodiments, the attachment G proteins are type II transmembrane glycoproteins containing an N-terminal cytoplasmic tail (e.g., corresponding to amino acids 1-49 of SEQ ID NO: 9266), a transmembrane domain (e.g., corresponding to amino acids 50-70 of SEQ ID NO: 9266), and an extracellular domain containing an extracellular stalk (e.g., corresponding to amino acids 71-187 of SEQ ID NO: 9266), and a globular head (corresponding to amino acids 188-602 of SEQ ID NO: 9266). In such embodiments, the N-terminal cytoplasmic domain is within the inner lumen of the lipid bilayer and the C-terminal portion is the extracellular domain that is exposed on the outside of the lipid bilayer. Regions of the stalk in the C-terminal region (e.g. corresponding to amino acids 159-167 of NiV-G) have been shown to be involved in interactions with F protein and triggering of F protein fusion (Liu et al. 2015 J of Virology 89:1838). In wild-type G protein, the globular head mediates receptor binding to henipavirus entry receptors eprhin B2 and ephrin B3, but is dispensable for membrane fusion (Brandel-Tretheway et al. Journal of Virology. 2019. 93(13)e00577-19). In particular embodiments herein, tropism of the G protein is altered by linkage of the G protein or biologically active fragment thereof (e.g. cytoplasmic truncation) to a sdAb variable domain. Binding of the G protein to a binding partner can trigger fusion mediated by a compatible F protein or a biologically active portion thereof. G protein sequences disclosed herein are predominantly disclosed as expressed sequences including an N-terminal methionine required for start of translation. As such N-terminal methionines are commonly cleaved co- or post-translationally, the mature protein sequences for all G protein sequences disclosed herein are also contemplated as lacking the N-terminal methionine.

G glycoproteins are highly conserved among henipavirus species. For example, the G proteins of NiV and HeV viruses share 79% amino acid identity. Studies have shown a high degree of compatibility among G proteins with F proteins of different species as demonstrated by heterotypic fusion activation (Brandel-Tretheway et al. Journal of Virology. 2019). As described further below, a targeted lipid particle can contain heterologous G and F proteins from different species.

In some embodiments, the G protein has a sequence set forth in any of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037, or is a functionally active variant or biologically active portion thereof that has a sequence that is at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% identical to any one of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037. In particular embodiments, the G protein or functionally active variant or biologically active portion is a protein that retains fusogenic activity in conjunction with a Henipavirus F protein, such as an F protein (e.g. NiV-F or HeV—F). Fusogenic activity includes the activity of the G protein in conjunction with a Henipavirus F protein to promote or facilitate fusion of two membrane lumens, such as the lumen of the targeted lipid particle having embedded in its lipid bilayer a henipavirus F and G protein, and a cytoplasm of a target cell, e.g. a cell that contains a surface receptor or molecule that is recognized or bound by the targeted envelope protein. In some embodiments, the F protein and G protein are from the same Henipavirus species (e.g. NiV-G and NiV-F). In some embodiments, the F protein and G protein are from different Henipavirus species (e.g. NiV-G and HeV-F).

In particular embodiments, the G protein has the sequence of amino acids set forth in SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037, or is a functionally active variant thereof or a biologically active portion thereof that retains fusogenic activity. In some embodiments, the functionally active variant comprises an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to any one of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037 and retains fusogenic activity in conjunction with a Henipavirus F protein (e.g., NiV-F or HeV-F). In some embodiments, the biologically active portion has an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to any one of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037 and retains fusogenic activity in conjunction with a Henipavirus F protein (e.g., NiV-F or HeV-F).

Reference to retaining fusogenic activity includes activity (in conjunction with a Henipavirus F protein) that is at or about 10% to at or about 150% or more of the level or degree of binding of the corresponding wild-type G protein, such as set forth in any one of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037, such as at least or at least about 10% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 15% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 20% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 25% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 30% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 35% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 40% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 45% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 50% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 55% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 60% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 65% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 70% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 75% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 80% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 85% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 90% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 95% of the level or degree of fusogenic activity of the corresponding wild-type G protein, such as at least or at least about 100% of the level or degree of fusogenic activity of the corresponding wild-type G protein, or such as at least or at least about 120% of the level or degree of fusogenic activity of the corresponding wild-type G protein.

In some embodiments, the G protein is a mutant G protein that is a functionally active variant or biologically active portion containing one or more amino acid mutations, such as one or more amino acid insertions, deletions, substitutions, or truncations. In some embodiments, the mutations described herein relate to amino acid insertions, deletions, substitutions, or truncations of amino acids compared to a reference G protein sequence. In some embodiments, the reference G protein sequence is the wild-type sequence of a G protein or a biologically active portion thereof. In some embodiments, the functionally active variant or the biologically active portion thereof is a mutant of a wild-type Hendra (HeV) virus G protein, a wild-type Nipah (NiV) virus G-protein (NiV-G), a wild-type Cedar (CedPV) virus G-protein, a wild-type Mojiang virus G-protein, a wild-type bat Paramyxovirus G-protein, or biologically active portions thereof. In some embodiments, the wild-type G protein has the sequence set forth in any one of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037.

In some embodiments, the G protein is a mutant G protein that is a biologically active portion that is an N-terminally and/or C-terminally truncated fragment of a wild-type Hendra (HeV) virus G protein, a wild-type Nipah (NiV) virus G-protein (NiV-G), a wild-type Cedar (CedPV) virus G-protein, a wild-type Mojiang virus G-protein, or a wild-type bat Paramyxovirus G-protein. In particular embodiments, the truncation is an N-terminal truncation of all or a portion of the cytoplasmic domain. In some embodiments, the mutant G protein is a biologically active portion that is truncated and lacks up to 49 contiguous amino acid residues at or near the N-terminus of the wild-type G protein, such as a wild-type G protein set forth in any one of SEQ ID NOs: 9266, 9274, 9285-9288, 9295, 9303, 9305-9037. In some embodiments, the mutant G protein is truncated and lacks up to 49 contiguous amino acids, such as up to 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 30, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 contiguous amino acid(s) at the N-terminus of the wild-type G protein.

In some embodiments, the G protein is a wild-type Nipah virus G (NiV-G) protein or a wild-type Hendra virus G protein, or is a functionally active variant or biologically active portion thereof. In some embodiments, the G protein is a NiV-G protein that has the sequence set forth in SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295, or is a functional variant or a biologically active portion thereof that has an amino acid sequence having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295.

In some embodiments, the G protein is a mutant NiV-G protein that is a biologically active portion of a wild-type NiV-G. In some embodiments, the biologically active portion is an N-terminally truncated fragment. In some embodiments, the mutant NiV-G protein is truncated and lacks up to 5 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 6 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 7 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 8 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 9 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 10 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 11 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 12 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 13 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9266, SEQ ID NO: 9285, or SEQ ID NO: 9295), up to 14 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 15 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 16 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 17 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 18 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 19 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 20 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 21 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 22 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 23 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 24 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 25 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 26 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 27 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 28 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 29 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 30 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 31 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 32 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 33 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 34 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 35 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 36 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 37 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 38 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 39 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 40 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 41 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 42 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 43 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295), up to 44 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 618, or SEQ ID NO: 628), or up to 45 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295).

In some embodiments, the NiV-G protein is a biologically active portion that does not contain a cytoplasmic domain. In some embodiments, the NiV-G protein without the cytoplasmic domain is encoded by SEQ ID NO:9289.

In some embodiments, the mutant NiV-G protein comprises a sequence set forth in any of SEQ ID NOs: 601-606, 629-634, 612, 622, or 637, or is a functional variant thereof that has an amino acid sequence having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, or at least at or about 87%, at least at or about 88%, or at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NOs: 9267-9269, 9296-9301, 9277, 9289, 9304.

In some embodiments, the mutant NiV-G protein has a 5 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295), such as set forth in SEQ ID NO:9267 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9267, or as set forth in SEQ ID NO:9296 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9296 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9296.

In some embodiments, the mutant NiV-G protein has a 10 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295), such as set forth in SEQ ID NO:9268 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9268, or such as set forth in SEQ ID NO:9297 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9297.

In some embodiments, the mutant NiV-G protein has a 15 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295), such as set forth in SEQ ID NO:9269 or a functional variant thereof that has an amino acid sequence having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9269, or such as set forth in SEQ ID NO:9298 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9298.

In some embodiments, the mutant NiV-G protein has a 20 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295) such as set forth in SEQ ID NO:9270, or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9270, or such as set forth in SEQ ID NO:9299 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9299.

In some embodiments, the mutant NiV-G protein has a 25 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295), such as set forth in SEQ ID NO:9271 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9271, or such as set forth in SEQ ID NO:9300 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9300.

In some embodiments, the mutant NiV-G protein has a 30 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295), such as set forth in SEQ ID NO:9273 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9273, or such as set forth in SEQ ID NO:9301 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9301.

In some embodiments, the mutant NiV-G protein has a 33 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295) or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9277, or such as set forth in SEQ ID NO:9302 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9302.

In some embodiments, the mutant NiV-G protein has a 34 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295), such as set forth in SEQ ID NO:9277 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9277, or such as set forth in SEQ ID NO:9302 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9302.

In a preferred embodiment, the NiV-G protein has a 34 amino acid truncation at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295) and one or more amino acid substitutions corresponding to amino acid substitutions selected from E501A, W504A, Q530A, and E533A with reference to the numbering set forth in SEQ ID NO:9285.

In some embodiments, the mutant NiV-G protein lacks the N-terminal cytoplasmic domain of the wild-type NiV-G protein (SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO: 9295), such as set forth in SEQ ID NO:9289 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9289.

In some embodiments, the mutant G protein is a mutant HeV-G protein that has the sequence set forth in SEQ ID NO:9275 or 9303, or is a functional variant or biologically active portion thereof that has an amino acid sequence having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9275 or 9303.

In some embodiments, the G protein is a mutant HeV-G protein that is a biologically active portion of a wild-type HeV-G. In some embodiments, the biologically active portion is an N-terminally truncated fragment. In some embodiments, the mutant HeV-G protein is truncated and lacks up to 5 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 6 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 7 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 8 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 9 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 10 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 11 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 12 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 13 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 14 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 15 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 16 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 17 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 18 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 19 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 20 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 21 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 22 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 23 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 24 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 25 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 26 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 27 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 28 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 29 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 30 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 31 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 32 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 33 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 34 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 35 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 36 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 37 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 38 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 39 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 40 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 41 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 42 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 43 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), up to 44 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303), or up to 45 contiguous amino acid residues at or near the N-terminus of the wild-type HeV-G protein (SEQ ID NO:9275 or 9303).

In some embodiments, the HeV-G protein is a biologically active portion that does not contain a cytoplasmic domain. In some embodiments, the mutant HeV-G protein lacks the N-terminal cytoplasmic domain of the wild-type HeV-G protein (SEQ ID NO: 9275 or 9303), such as set forth in SEQ ID NO:9303 or a functional variant thereof having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9303.

In some embodiments, the G protein or the functionally active variant or biologically active portion thereof binds to Ephrin B2 or Ephrin B3. In some aspects, the G protein has the sequence of amino acids set forth in any one of SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO: 9287, or SEQ ID NO:9288, or is a functionally active variant thereof or a biologically active portion thereof that is able to bind to Ephrin B2 or Ephrin B3. In some embodiments, the functionally active variant or biologically active portion has an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO: 9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, and retains binding to Ephrhin B2 or B3.

Reference to retaining binding to Ephrin B2 or B3 includes binding that is at least or at least about 5% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 10% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO: 9295, SEQ ID NO: 9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 15% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 20% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 25% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO: 9295, SEQ ID NO: 9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion, 30% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO: 9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO: 9288, or a functionally active variant or biologically active portion thereof, 35% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 40% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 45% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 50% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO: 9295, SEQ ID NO: 9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 55% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO: 9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 60% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, 65% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO: 9295, SEQ ID NO: 9287, or SEQ ID NO: 9288, or a functionally active variant or biologically active portion thereof, 70% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO: 9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, such as at least or at least about 75% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO: 9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, such as at least or at least about 80% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, such as at least or at least about 85% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, such as at least or at least about 90% of the level or degree of binding of the corresponding wild-type G protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO: 9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof, or such as at least or at least about 95% of the level or degree of binding of the corresponding wild-type protein, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9275, SEQ ID NO:9285, SEQ ID NO:9286, SEQ ID NO:9295, SEQ ID NO:9287, or SEQ ID NO:9288, or a functionally active variant or biologically active portion thereof. In some embodiments, the G protein is NiV-G or a functionally active variant or biologically active portion thereof and binds to Ephrin B2 or Ephrin B3.

In some aspects, the NiV-G has the sequence of amino acids set forth in SEQ ID NO: 9266, SEQ ID NO:9285, or SEQ ID NO:9295, or is a functionally active variant thereof or a biologically active portion thereof that is able to bind to Ephrin B2 or Ephrin B3. In some embodiments, the functionally active variant or biologically active portion has an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO: 9295 and retains binding to Eprhin B2 or B3. Exemplary biologically active portions include N-terminally truncated variants lacking all or a portion of the cytoplasmic domain, e.g. 1 or more, such as 1 to 49 contiguous N-terminal amino acid residues, e.g. set forth in any one of SEQ ID NOS: 9267-9272, 9289, and 9296-9301.

Reference to retaining binding to Ephrin B2 or B3 includes binding that is at least or at least about 5% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295, 10% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295, 15% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295, 20% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9285, or SEQ ID NO:92954, 25% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295, 30% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in S SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, 35% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO: 9295, 40% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO: 9295, 45% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, 50% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, 55% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, 60% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, 65% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, 70% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, such as at least or at least about 75% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9285, or SEQ ID NO:9295, such as at least or at least about 80% of the level or degree of binding of the corresponding wild-type NIV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO:9295, such as at least or at least about 85% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO:9285, or SEQ ID NO: 9295, such as at least or at least about 90% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO:9266, SEQ ID NO: 9285, or SEQ ID NO:9295, or such as at least or at least about 95% of the level or degree of binding of the corresponding wild-type NiV-G, such as set forth in SEQ ID NO: 9266, SEQ ID NO:9285, or SEQ ID NO:9295.

In some embodiments, the G protein is HeV-G or a functionally active variant or biologically active portion thereof and binds to Ephrin B2 or Ephrin B3. In some aspects, the HeV-G has the sequence of amino acids set forth in SEQ ID NO:9275 or 9303, or is a functionally active variant thereof or a biologically active portion thereof that is able to bind to Ephrin B2 or Ephrin B3. In some embodiments, the functionally active variant or biologically active portion has an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9275 or 9303 and retains binding to Eprhin B2 or B3. Exemplary biologically active portions include N-terminally truncated variants lacking all or a portion of the cytoplasmic domain, e.g. 1 or more, such as 1 to 49 contiguous N-terminal amino acid residues, e.g. set forth in any one of SEQ ID NO:9290.

Reference to retaining binding to Ephrin B2 or B3 includes binding that is at least or at least about 5% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 10% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 15% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 20% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 25% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 30% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 35% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 40% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 45% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 50% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 55% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 60% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 65% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, 70% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, such as at least or at least about 75% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, such as at least or at least about 80% of the level or degree of binding of the corresponding wild-type NIV-G, such as set forth in SEQ ID NO:9275 or 9303, such as at least or at least about 85% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, such as at least or at least about 90% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303, or such as at least or at least about 95% of the level or degree of binding of the corresponding wild-type HeV-G, such as set forth in SEQ ID NO:9275 or 9303.

In some embodiments, the G protein or the biologically thereof is a mutant G protein that exhibits reduced binding for the native binding partner of a wild-type G protein. In some embodiments, the mutant G protein or the biologically active portion thereof is a mutant of wild-type Niv-G and exhibits reduced binding to one or both of the native binding partners Ephrin B2 or Ephrin B3. In some embodiments, the mutant G-protein or the biologically active portion, such as a mutant NiV-G protein, exhibits reduced binding to the native binding partner. In some embodiments, the reduced binding to Ephrin B2 or Ephrin B3 is reduced by greater than at or about 5%, at or about 10%, at or about 15%, at or about 20%, at or about 25%, at or about 30%, at or about 40%, at or about 50%, at or about 60%, at or about 70%, at or about 80%, at or about 90%, or at or about 100%.

In some embodiments, the mutations described herein improve transduction efficiency. In some embodiments, the mutations described herein allow for specific targeting of other desired cell types that are not Ephrin B2 or Ephrin B3. In some embodiments, the mutations described herein result in at least the partial inability to bind at least one natural receptor, such as to reduce the binding to at least one of Ephrin B2 or Ephrin B3. In some embodiments, the mutations described herein interfere with natural receptor recognition.

In some embodiments, the mutant NiV-G protein or the biologically active portion thereof is truncated and lacks up to 5 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 6 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 7 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 8 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 9 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 10 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 11 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 12 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 13 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 14 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 15 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 16 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 17 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 18 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 19 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 20 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 21 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 22 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 23 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 24 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 25 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 26 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 27 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 28 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 29 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 30 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 31 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 32 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 33 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 34 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 35 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 36 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), 37 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 38 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285), 39 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO: 9285), or 40 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein (SEQ ID NO:9285).

In some embodiments, the G protein contains one or more amino acid substitutions in a residue that is involved in the interaction with one or both of Ephrin B2 and Ephrin B3. In some embodiments, the amino acid substitutions correspond to mutations E501A, W504A, Q530A, and E533A with reference to numbering set forth in SEQ ID NO:9285.

In some embodiments, the G protein is a mutant G protein containing one or more amino acid substitutions selected from the group consisting of E501A, W504A, Q530A, and E533A with reference to numbering set forth in SEQ ID NO:9285. In some embodiments, the G protein is a mutant G protein that contains one or more amino acid substitutions selected from the group consisting of E501A, W504A, Q530A, and E533A with reference to SEQ ID NO:9285 or a biologically active portion thereof containing an N-terminal truncation. In some embodiments, the G protein is a mutant G protein that contains one or more amino acid substitutions selected from the group consisting of E501A, W504A, Q530A, and E533A in combination with any one of the N-terminal truncations disclosed above with reference to SEQ ID NO:9285 or a biologically active portion thereof. In some embodiments, any of the mutant G proteins described above contains one, two, three, or all four amino acid selected from the group consisting of E501A, W504A, Q530A, and E533A with reference to numbering set forth in SEQ ID NO:9285, in all pairwise and triple combinations thereof.

In some embodiments, the mutant NiV-G protein has the amino acid sequence set forth in SEQ ID NO:9273 or 9302 or an amino acid sequence having at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9273 or 9302. In particular embodiments, the G protein has the sequence of amino acids set forth in SEQ ID NO:9273 or 9302.

In some embodiments, the targeted envelope protein contains a G protein or a functionally active variant or biologically active portion thereof and an sdAb variable domain, in which the targeted envelope protein exhibits increased binding for another molecule that is different from the native binding partner of a wild-type G protein. In some embodiments, the other molecule is a protein expressed on the surface of desired target cell. In some embodiments, the increased binding to the other molecule is increased by greater than at or about 25%, at or about 30%, at or about 40%, at or about 50%, at or about 60%, at or about 70%, at or about 80%, at or about 90%, or at or about 100%. In particular embodiments, the binding confers re-targeted binding compared to the binding of a wild-type G protein in which a new or different binding activity is conferred.

In some embodiments, the C-terminus of the single domain antibody is attached to the C-terminus of the G protein or biologically active portion thereof. In some embodiments, the N-terminus of the single domain antibody is exposed on the exterior surface of the lipid bilayer. In some embodiments, the N-terminus of the single domain antibody binds to a cell surface molecule of a target cell. In some embodiments, the single domain antibody specifically binds to a cell surface molecule present on a target cell. In some embodiments, the cell surface molecule is a protein, glycan, lipid, or low molecular weight molecule.

In some embodiments, the cell surface molecule of a target cell is an antigen or portion thereof. In some embodiments, the single domain antibody or portion thereof is an antibody having a single monomeric domain antigen binding/recognition domain that is able to bind selectively to a specific antigen. In some embodiments, the single domain antibody binds an antigen present on a target cell.

Exemplary cells include immune effector cells, peripheral blood mononuclear cells (PBMCs) such as lymphocytes (T cells, B cells, natural killer cells) and monocytes, granulocytes (neutrophils, basophils, eosinophils), macrophages, dendritic cells, cytotoxic T lymphocytes, polymorphonuclear cells (also known as PMNs, PMLs, or PMNLs), stem cells, embryonic stem cells (ESs or ECSs), neural stem cells, mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), human myogenic stem cells, muscle-derived stem cells (MuStem), limbal epithelial stem cells, cardio-myogenic stem cells, cardiomyocytes, progenitor cells, allogenic cells, resident cardiac cells, induced pluripotent stem cells (iPSs or iPSCs), adipose-derived or phenotypic modified stem or progenitor cells, CD133+ cells, aldehyde dehydrogenase-positive cells (ALDH+), umbilical cord blood (UCB) cells, peripheral blood stem cells (PBSCs), neurons, neural progenitor cells, pancreatic beta cells, glial cells, or hepatocytes.

In some embodiments, the target cell is a cell of a target tissue. The target tissue can include liver, lungs, heart, spleen, pancreas, gastrointestinal tract, kidney, testes, ovaries, brain, reproductive organs, central nervous system, peripheral nervous system, skeletal muscle, endothelium, inner ear, or eye.

In some embodiments, the target cell is a muscle cell (e.g., skeletal muscle cell), kidney cell, liver cell (e.g. hepatocyte), or a cardiac cell (e.g. cardiomyocyte). In some embodiments, the target cell is a cardiac cell, e.g., a cardiomyocyte (e.g., a quiescent cardiomyocyte), a hepatoblast (e.g., a bile duct hepatoblast), an epithelial cell, a T cell (e.g. a naive T cell), a macrophage (e.g., a tumor infiltrating macrophage), or a fibroblast (e.g., a cardiac fibroblast).

In some embodiments, the target cell is a tumor-infiltrating lymphocyte, a T cell, a neoplastic or tumor cell, a virus-infected cell, a stem cell, a central nervous system (CNS) cell, a hematopoietic stem cell (HSC), a liver cell or a fully differentiated cell. In some embodiments, the target cell is a CD3+ T cell, a CD4+ T cell, a CD8+ T cell, a hepatocyte, a hematopoietic stem cell, a CD34+ hematopoietic stem cell, a CD105+ hematopoietic stem cell, a CD117+ hematopoietic stem cell, a CD105+ endothelial cell, a B cell, a CD20+ B cell, a CD19+ B cell, a cancer cell, a CD133+ cancer cell, an EpCAM+ cancer cell, a CD19+ cancer cell, a Her2/Neu+ cancer cell, a GluA2+ neuron, a GluA4+ neuron, a NKG2D+ natural killer cell, a SLC1A3+ astrocyte, a SLC7A10+ adipocyte, or a CD30+ lung epithelial cell.

In some embodiments, the target cell is an antigen presenting cell, an MHC class II+ cell, a professional antigen presenting cell, an atypical antigen presenting cell, a macrophage, a dendritic cell, a myeloid dendritic cell, a plasmacytoid dendritic cell, a CD11c+ cell, a CD11b+ cell, a splenocyte, a B cell, a hepatocyte, a endothelial cell, or a non-cancerous cell. In some embodiments, the cell surface molecule is any one of CD4.

In some embodiments, the G protein or functionally active variant or biologically active portion thereof is linked directly to the sdAb variable domain (e.g., a VHH) or scFv. In some embodiments, the targeted envelope protein is a fusion protein that has the following structure: (N′-single domain antibody-C′)-(C′-G protein-N′). In some embodiments, the targeted envelope protein is a fusion protein that has the following structure: (N′-scFv-C′)-(C′-G protein-N′).

In some embodiments, the G protein or functionally active variant or biologically active portion thereof is linked indirectly via a linker to the sdAb variable domain or scFv. In some embodiments, the linker is a peptide linker, such as a polypeptide linker. In some embodiments, the linker is a chemical linker.

In some embodiments, the linker is a peptide linker and the targeted envelope protein is a fusion protein containing the G protein or functionally active variant or biologically active portion thereof linked via a peptide linker to the sdAb variable domain or svFv. In some embodiments, the targeted envelope protein is a fusion protein that has the following structure: (N′-single domain antibody-C′)-Linker-(C′-G protein-N′). In some embodiments, the targeted envelope protein is a fusion protein that has the following structure: (N′-scFv-C′)-Linker-(C′-G protein-N′). In some embodiments, the peptide linker is a polypeptide linker up to 65 amino acids in length. In some embodiments, the peptide linker comprises from or from about 2 to 65 amino acids, 2 to 60 amino acids, 2 to 56 amino acids, 2 to 52 amino acids, 2 to 48 amino acids, 2 to 44 amino acids, 2 to 40 amino acids, 2 to 36 amino acids, 2 to 32 amino acids, 2 to 28 amino acids, 2 to 24 amino acids, 2 to 20 amino acids, 2 to 18 amino acids, 2 to 14 amino acids, 2 to 12 amino acids, 2 to 10 amino acids, 2 to 8 amino acids, 2 to 6 amino acids, 6 to 65 amino acids, 6 to 60 amino acids, 6 to 56 amino acids, 6 to 52 amino acids, 6 to 48 amino acids, 6 to 44 amino acids, 6 to 40 amino acids, 6 to 36 amino acids, 6 to 32 amino acids, 6 to 28 amino acids, 6 to 24 amino acids, 6 to 20 amino acids, 6 to 18 amino acids, 6 to 14 amino acids, 6 to 12 amino acids, 6 to 10 amino acids, 6 to 8 amino acids, 8 to 65 amino acids, 8 to 60 amino acids, 8 to 56 amino acids, 8 to 52 amino acids, 8 to 48 amino acids, 8 to 44 amino acids, 8 to 40 amino acids, 8 to 36 amino acids, 8 to 32 amino acids, 8 to 28 amino acids, 8 to 24 amino acids, 8 to 20 amino acids, 8 to 18 amino acids, 8 to 14 amino acids, 8 to 12 amino acids, 8 to 10 amino acids, 10 to 65 amino acids, 10 to 60 amino acids, 10 to 56 amino acids, 10 to 52 amino acids, 10 to 48 amino acids, 10 to 44 amino acids, 10 to 40 amino acids, 10 to 36 amino acids, 10 to 32 amino acids, 10 to 28 amino acids, 10 to 24 amino acids, 10 to 20 amino acids, 10 to 18 amino acids, 10 to 14 amino acids, 10 to 12 amino acids, 12 to 65 amino acids, 12 to 60 amino acids, 12 to 56 amino acids, 12 to 52 amino acids, 12 to 48 amino acids, 12 to 44 amino acids, 12 to 40 amino acids, 12 to 36 amino acids, 12 to 32 amino acids, 12 to 28 amino acids, 12 to 24 amino acids, 12 to 20 amino acids, 12 to 18 amino acids, 12 to 14 amino acids, 14 to 65 amino acids, 14 to 60 amino acids, 14 to 56 amino acids, 14 to 52 amino acids, 14 to 48 amino acids, 14 to 44 amino acids, 14 to 40 amino acids, 14 to 36 amino acids, 14 to 32 amino acids, 14 to 28 amino acids, 14 to 24 amino acids, 14 to 20 amino acids, 14 to 18 amino acids, 18 to 65 amino acids, 18 to 60 amino acids, 18 to 56 amino acids, 18 to 52 amino acids, 18 to 48 amino acids, 18 to 44 amino acids, 18 to 40 amino acids, 18 to 36 amino acids, 18 to 32 amino acids, 18 to 28 amino acids, 18 to 24 amino acids, 18 to 20 amino acids, 20 to 65 amino acids, 20 to 60 amino acids, 20 to 56 amino acids, 20 to 52 amino acids, 20 to 48 amino acids, 20 to 44 amino acids, 20 to 40 amino acids, 20 to 36 amino acids, 20 to 32 amino acids, 20 to 28 amino acids, 20 to 26 amino acids, 20 to 24 amino acids, 24 to 65 amino acids, 24 to 60 amino acids, 24 to 56 amino acids, 24 to 52 amino acids, 24 to 48 amino acids, 24 to 44 amino acids, 24 to 40 amino acids, 24 to 36 amino acids, 24 to 32 amino acids, 24 to 30 amino acids, 24 to 28 amino acids, 28 to 65 amino acids, 28 to 60 amino acids, 28 to 56 amino acids, 28 to 52 amino acids, 28 to 48 amino acids, 28 to 44 amino acids, 28 to 40 amino acids, 28 to 36 amino acids, 28 to 34 amino acids, 28 to 32 amino acids, 32 to 65 amino acids, 32 to 60 amino acids, 32 to 56 amino acids, 32 to 52 amino acids, 32 to 48 amino acids, 32 to 44 amino acids, 32 to 40 amino acids, 32 to 38 amino acids, 32 to 36 amino acids, 36 to 65 amino acids, 36 to 60 amino acids, 36 to 56 amino acids, 36 to 52 amino acids, 36 to 48 amino acids, 36 to 44 amino acids, 36 to 40 amino acids, 40 to 65 amino acids, 40 to 60 amino acids, 40 to 56 amino acids, 40 to 52 amino acids, 40 to 48 amino acids, 40 to 44 amino acids, 44 to 65 amino acids, 44 to 60 amino acids, 44 to 56 amino acids, 44 to 52 amino acids, 44 to 48 amino acids, 48 to 65 amino acids, 48 to 60 amino acids, 48 to 56 amino acids, 48 to 52 amino acids, 50 to 65 amino acids, 50 to 60 amino acids, 50 to 56 amino acids, 50 to 52 amino acids, 54 to 65 amino acids, 54 to 60 amino acids, 54 to 56 amino acids, 58 to 65 amino acids, 58 to 60 amino acids, or 60 to 65 amino acids. In some embodiments, the peptide linker is a peptide that is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, or 65 amino acids in length.

In particular embodiments, the linker is a flexible peptide linker. In some such embodiments, the linker is 1-20 amino acids, such as 1-20 amino acids predominantly composed of glycine. In some embodiments, the linker is 1-20 amino acids, such as 1-20 amino acids predominantly composed of glycine and serine. In some embodiments, the linker is a flexible peptide linker containing amino acids Glycine and Serine, referred to as GS-linkers. In some embodiments, the peptide linker includes the sequences GS, GGS, GGGGS (SEQ ID NO:9294), GGGGGS (SEQ ID NO:9292) or combinations thereof. In some embodiments, the peptide linker is a polypeptide linker that has the sequence (GGS) n (SEQ ID NO: 14126), wherein n is 1 to 10. In some embodiments, the peptide linker is a polypeptide linker that has the sequence (GGGGS) n, (SEQ ID NO:9293) wherein n is 1 to 10. In some embodiments, the peptide linker is a polypeptide linker that has the sequence (GGGGGS) n (SEQ ID NO:9284), wherein n is 1 to 6.

Also provided herein are polynucleotides comprising a nucleic acid sequence encoding a targeted envelope protein. In some embodiments, the polynucleotides comprise a nucleic acid sequence encoding a G protein or biologically active portion thereof. In some embodiments, the polynucleotides further comprise a nucleic acid sequence encoding a single domain antibody (sdAb) variable domain or scFv or biologically active portion thereof. The polynucleotides may include a sequence of nucleotides encoding any of the targeted envelope proteins described above. The polynucleotide can be a synthetic nucleic acid. Also provided are expression vectors containing any of the provided polynucleotides.

In some of any embodiments, expression of natural or synthetic nucleic acids is typically achieved by operably linking a nucleic acid encoding the gene of interest to a promoter and incorporating the construct into an expression vector. In some embodiments, vectors are suitable for replication and integration in eukaryotes. In some embodiments, cloning vectors contain transcription and translation terminators, initiation sequences, and promoters useful for expression of the desired nucleic acid sequence. In some of any embodiments described herein, a plasmid comprises a promoter suitable for expression in a cell.

In some embodiments, the polynucleotides contain at least one promoter that is operatively linked to control expression of the targeted envelope protein containing the G protein and the single domain antibody (sdAb) variable domain or scFv. For expression of the targeted envelope protein, at least one element in each promoter functions to position the start site for RNA synthesis. The best-known example of this is the TATA box, but in some promoters lacking a TATA box, such as the promoter for the mammalian terminal deoxynucleotidyl transferase gene and the promoter for the SV40 genes, a discrete element overlying the start site itself helps to fix the place of initiation.

In some embodiments, additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. In some embodiments, additional promoter elements are located in the region 30-110 bp upstream of the start site, although a number of promoters have been shown to contain functional elements downstream of the start site as well. In some embodiments, spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In some embodiments, such as with the thymidine kinase (tk) promoter, the spacing between promoter elements is increased to 50 bp apart before activity begins to decline. In some embodiments, depending on the promoter, individual elements function either cooperatively or independently to activate transcription.

A promoter may be one naturally associated with a gene or polynucleotide sequence, as may be obtained by isolating the 5′ non-coding sequences located upstream of the coding segment and/or exon. Such a promoter can be referred to as “endogenous.” Similarly, an enhancer may be one naturally associated with a polynucleotide sequence, located either downstream or upstream of that sequence. Alternatively, certain advantages will be gained by positioning the coding polynucleotide segment under the control of a recombinant or heterologous promoter, which refers to a promoter that is not normally associated with a polynucleotide sequence in its natural environment. A recombinant or heterologous enhancer refers also to an enhancer not normally associated with a polynucleotide sequence in its natural environment. Such promoters or enhancers may include promoters or enhancers of other genes, and promoters or enhancers isolated from any other prokaryotic, viral, or eukaryotic cell, and promoters or enhancers not “naturally occurring,” i.e., containing different elements of different transcriptional regulatory regions, and/or mutations that alter expression. In addition to producing nucleic acid sequences of promoters and enhancers synthetically, sequences may be produced using recombinant cloning and/or nucleic acid amplification technology, including PCR, in connection with the compositions disclosed herein.

In some embodiments, a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. In some embodiments, the promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. In some embodiments, a suitable promoter is Elongation Growth Factor-la (EF-I a). In some embodiments, other constitutive promoter sequences are also used, including, but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter.

In some embodiments, the promoter is an inducible promoter. In some embodiments, the inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence to which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. In some embodiments, inducible promoters comprise a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter.

In some embodiments, exogenously controlled inducible promoters are used to regulate expression of the G protein and single domain antibody (sdAb) variable domain or scFv. For example, radiation-inducible promoters, heat-inducible promoters, and/or drug-inducible promoters can be used to selectively drive transgene expression in, for example, targeted regions. In such embodiments, the location, duration, and level of transgene expression is regulated by the administration of the exogenous source of induction.

In some embodiments, expression of the targeted envelope protein containing a G protein and single domain antibody (sdAb) variable domain or scFv is regulated using a drug-inducible promoter. For example, in some cases, the promoter, enhancer, or transactivator comprises a Lac operator sequence, a tetracycline operator sequence, a galactose operator sequence, a doxycycline operator sequence, a rapamycin operator sequence, a tamoxifen operator sequence, or a hormone-responsive operator sequence, or an analog thereof. In some instances, the inducible promoter comprises a tetracycline response element (TRE). In some embodiments, the inducible promoter comprises an estrogen response element (ERE), which can activate gene expression in the presence of tamoxifen. In some instances, a drug-inducible element, such as a TRE, is combined with a selected promoter to enhance transcription in the presence of drug, such as doxycycline. In some embodiments, the drug-inducible promoter is a small molecule-inducible promoter.

Any of the provided polynucleotides can be modified to remove CpG motifs and/or to optimize codons for translation in a particular species, such as human, canine, feline, equine, ovine, bovine, etc. species. In some embodiments, the polynucleotides are optimized for human codon usage (i.e., human codon-optimized). In some embodiments, the polynucleotides are modified to remove CpG motifs. In other embodiments, the provided polynucleotides are modified to remove CpG motifs and are codon-optimized, such as human codon-optimized. Methods of codon optimization and CpG motif detection and modification are well-known. Typically, polynucleotide optimization enhances transgene expression, increases transgene stability and preserves the amino acid sequence of the encoded polypeptide.

In order to assess the expression of the targeted envelope protein, the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing particles, e.g. viral particles. In other embodiments, the selectable marker is carried on a separate piece of DNA and used in a co-transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers are known in the art and include, for example, antibiotic-resistance genes, such as neo and the like.

Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. Reporter genes that encode for easily assayable proteins are well known in the art. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a protein whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells.

Suitable reporter genes may include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (see, e.g., Ui-Tei et al., 2000, FEBS Lett. 479:79-82). Suitable expression systems are well known and may be prepared using well known techniques or obtained commercially. Internal deletion constructs may be generated using unique internal restriction sites or by partial digestion of non-unique restriction sites. Constructs may then be transfected into cells that display high levels of the desired polynucleotide and/or polypeptide expression. In general, the construct with the minimal 5′ flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription.

Lipid Particles Targeting CD4

Also provided herein are targeted lipid particles (e.g. targeting CD4), such as targeted viral vectors, that comprise a F protein molecule or biologically active portion thereof of the Paramyxoviridae family, and a fusion protein comprising (i) an envelope attachment glycoprotein G (G protein), hemagglutinin (H Protein), or hemagglutinin-neuraminidase (HN Protein), or a biologically active portion thereof of the Paramyxoviridae family, and (ii) a single domain antibody (sdAb) variable domain or scFv, wherein the single domain antibody variable domain or scFv is attached to the C-terminus of the G protein or the biologically active portion, wherein each is exposed on the outer surface of the targeted lipid particle. In particular embodiments, the provided targeted lipid particles exhibit fusogenic activity, which is mediated by the targeted envelope protein that facilitates binding to a target cell and contains the G protein or biologically active portion thereof, and the F protein or biologically active portion thereof that is involved in facilitating the merger or fusion of the two lumens of the lipid particle and the target cell membranes. Table 25 provides non-limiting examples of G and F proteins for use in the targeted lipid particles of the disclosure.

In some embodiments, the targeted lipid particle provided herein (e.g. targeted lentiviral vector) has increased or greater expression of the targeted envelope protein compared to a reference lipid particle (e.g. reference lentiviral vector) that incorporates a similar envelope protein but that is fused to an alternative targeting moiety other than a sdAb variable domain, such as a single chain variable fragment (scFv). In some embodiments, the targeted lipid particles are produced by pseudotyping of viral vectors (e.g lentiviral particles) following co-transfection of the packaging cells with the transfer, envelope, and gag-pol plasmids.

In some embodiments, the expression is increased by at or greater than 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 200%, 300%, 400%, 500% or more, compared to a reference lipid particle (e.g. reference lentiviral vector), e.g. a reference lipid particle containing a similar envelope protein but that is fused to an scFv. In some examples, the expression is increased by at or greater than 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold or more, compared to a reference lipid particle (e.g. reference lentiviral vector), e.g. a reference lipid particle containing a similar envelope protein but that is fused to an scFv. In some embodiments, expression is assayed in vitro using flow cytometry, e.g. FACs. In some embodiments, expression can be depicted as the number or density of targeted envelope protein on the surface of a targeted lipid particle (e.g. targeted lentiviral vector). In some embodiments, expression is depicted as the mean fluorescent intensity (MFI) of surface expression of the targeted envelope protein on the surface of a targeted lipid particle (e.g. targeted lentiviral vector). In some embodiments, expression is depicted as the percent of lipid particle (e.g. lentiviral vectors) in a population that are surface positive for the targeted envelope protein.

In some embodiments, in a population of targeted lipid particles (e.g. targeted lentiviral vectors) greater than at or about 50% of the lipid particles are surface positive for the targeted envelope protein. For example, in a population of provided targeted lipid particle (e.g. targeted lentiviral vectors) greater than at or about 55%, greater than at or about 60%, greater than at or about 65%, greater than at or about 70%, or greater than at or about 75% of the viral vectors in the population are surface positive for the targeted envelope protein.

In some embodiments, titer of the targeted lipid particles following introduction into target cells, such as by transduction (e.g. transduced cells), is increased compared to titer into the same target cells of reference lipid particles (e.g. reference lentiviral vector) that incorporate a similar envelope protein but fused to an alternative targeting moiety other than a sdAb variable domain, such as a single chain variable fragment (scFv). Typically, the alternative targeting moiety recognizes or binds the same target molecule as the sdAb variable domain of the targeted envelope protein of the targeted lipid particles. In some embodiments, the titer is increased by at or greater than 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 200%, 300%, 400%, 500% or more, compared to titer of a reference lipid particle (e.g. reference lentiviral vector), e.g. a reference lipid particle containing a similar envelope protein but that is fused to an scFv. In some examples, the titer is increased by at or greater than 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 30-fold or more, compared to the titer of a reference lipid particle (e.g. reference lentiviral vector), e.g. a reference viral vector containing a similar envelope protein but that is fused to an scFv. In some embodiments, the titer of the targeted lipid particles in target cells (e.g. transduced cells) is greater than at or about 1×10⁶ transduction units (TU)/mL. For example, the titer of the targeted lipid particles in target cells (e.g. transduced cells) is greater than at or about 2×10⁶ TU/mL, greater than at or about 3×10⁶ TU/mL, greater than at or about 4×10⁶ TU/mL, greater than at or about 5×10⁶ TU/mL, greater than at or about 6×10⁶ TU/mL, greater than at or about 7×10⁶ TU/mL, greater than at or about 8×10⁶ TU/mL, greater than at or about 9×10⁶ TU/mL, or greater than at or about 1×10⁷ TU/mL.

A. F Proteins

In some embodiments, the targeted lipid particle comprises one or more fusogens, e.g. F proteins of the Paramyxoviridae family. In some embodiments, the targeted lipid particle contains an exogenous or overexpressed fusogen. In some embodiments, the fusogen is disposed in the lipid bilayer. In some embodiments, the fusogen facilitates the fusion of the targeted particle's lipid bilayer to a membrane. In some embodiments, the membrane is a plasma cell membrane.

In some embodiments, fusogens comprise protein based, lipid based, and chemical based fusogens. In some embodiments, the targeted lipid particle comprises a first fusogen comprising a protein fusogen and a second fusogen comprising a lipid fusogen or chemical fusogen. In some embodiments, the fusogen binds a fusogen binding partner on a target cell surface.

In some embodiments, the fusogen comprises a protein with a hydrophobic fusion polypeptide domain. In some embodiments the fusogen comprises an F protein of the Paramyxoviridae family. In some embodiments the fusogen contains a Nipah virus protein F, a measles virus F protein, a tupaia paramyxovirus F protein, a paramyxovirus F protein, a Hendra virus F protein, a Henipavirus F protein, a Morbilivirus F protein, a respirovirus F protein, a Sendai virus F protein, a rubulavirus F protein, or an avulavirus F protein, or a biologically active portion thereof.

In some embodiments, the fusion protein is a hemagglutinin-neuraminidase (HN) of the Paramyxoviridae family and/or F protein of the Paramyxoviridae family. In some embodiments, the respiratory paramyxovirus is a Sendai virus. The HN and F glycoproteins of Sendai viruses function to attach to sialic acids via the HN protein, and to mediate cell fusion for entry to cells via the F protein. In some embodiments, the fusion protein is a F and/or HN protein from the murine parainfluenza virus type 1 (See e.g., U.S. Pat. No. 10,704,061).

In some embodiments, the N-terminal hydrophobic fusion polypeptide domain of the F protein molecule or biologically active portion thereof is exposed on the outside of a lipid bilayer.

F proteins of henipaviruses are encoded as F₀ precursors containing a signal polypeptide (e.g. corresponding to amino acid residues 1-26 of SEQ ID NO: 592). Following cleavage of the signal polypeptide, the mature F₀ (e.g. SEQ ID NO: 593) is transported to the cell surface, then endocytosed and cleaved by cathepsin L (e.g. between amino acids 109-110 of SEQ ID NO: 592) into the mature fusogenic subunits F1 (e.g. corresponding to amino acids 110-546 of SEQ ID NO:9258; set forth in SEQ ID NO:9261) and F2 (e.g. corresponding to amino acid residues 27-109 of SEQ ID NO:1; set forth in SEQ ID NO:9260). The F1 and F2 subunits are associated by a disulfide bond and recycled back to the cell surface. The F1 subunit contains the fusion polypeptide domain located at the N terminus of the F1 subunit (e.g., corresponding to amino acids 110-129 of SEQ ID NO:9258) where it is able to insert into a cell membrane to drive fusion. In some cases, fusion activity is blocked by association of the F protein with G protein, until G engages with a target molecule resulting in its disassociation from F and exposure of the fusion polypeptide to mediate membrane fusion.

Among different henipavirus species, the sequence and activity of the F protein is highly conserved. For example, the F protein of NiV and HeV viruses share 89% amino acid sequence identity. Further, in some cases, the henipavirus F proteins exhibit compatibility with G proteins from other species to trigger fusion (Brandel-Tretheway et al. Journal of Virology. 2019. 93(13):e00577-19). In some aspects of the provided targeted lipid particle, the F protein is heterologous to the G protein, i.e., the F and G protein or biologically active portions thereof are from different henipavirus species. For example, the F protein is from Hendra virus and the G protein is from Nipah virus. In other aspects, the F protein can be a chimeric F protein containing regions of F proteins from different species of Henipavirus. In some embodiments, switching a region of amino acid residues of the F protein from one species of Henipavirus to another can result in fusion to the G protein of the species comprising the amino acid insertion. (Brandel-Tretheway et al. 2019). In some cases, the chimeric F protein contains an extracellular domain from one henipavirus species and a transmembrane and/or cytoplasmic domain from a different henipavirus species. For example, the F protein may contain an extracellular domain of Hendra virus and a transmembrane/cytoplasmic domain of Nipah virus. F protein sequences disclosed herein are predominantly disclosed as expressed sequences including an N-terminal signal sequence. Such N-terminal signal sequences are commonly cleaved co- or post-translationally, thus the mature protein sequences for all F protein sequences disclosed herein are also contemplated as lacking the N-terminal signal sequence.

In some embodiments, the F protein is encoded by a polynucleotide sequence that encodes the sequence set forth by any one of SEQ ID NOs: 592, 593, 608, 614-616, or 641-644, or is a functionally active variant or a biologically active portion thereof that has a sequence that is at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% identical to any one of SEQ ID NOS: 592, 593, 608, 614-616, or 641-644. In particular embodiments, the F protein or the functionally active variant or biologically active portion thereof retains fusogenic activity in conjunction with a Henipavirus G protein, such as a G protein set forth herein. Fusogenic activity includes the activity of the F protein in conjunction with a Henipavirus G protein to promote or facilitate fusion of two membrane lumens, such as the lumen of the targeted lipid particle having embedded in its lipid bilayer a henipavirus F and G protein, and a cytoplasm of a target cell, e.g., a cell that contains a surface receptor or molecule that is recognized or bound by the targeted envelope protein. In some embodiments, the F protein and G protein are from the same Henipavirus species (e.g. NiV-G and NiV-F). In some embodiments, the F protein and G protein are from different Henipavirus species (e.g., NiV-G and HeV-F). In particular embodiments, the F protein of the functionally active variant or biologically active portion retains the cleavage site cleaved by cathepsin L (e.g., corresponding to the cleavage site between amino acids 109-110 of SEQ ID NO:9258).

In particular embodiments, the F protein has the sequence of amino acids set forth in SEQ ID NO:9258, SEQ ID NO:9259, SEQ ID NO:9274, SEQ ID NO:9281, SEQ ID NO: 9282, SEQ ID NO:9283, SEQ ID NO:9308, SEQ ID NO:9309, SEQ ID NO:9310, or SEQ ID NO:9311 or is a functionally active variant thereof or a biologically active portion thereof that retains fusogenic activity. In some embodiments, the functionally active variant comprises an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9258, SEQ ID NO:9259, SEQ ID NO:9274, SEQ ID NO:9281, SEQ ID NO:9282, SEQ ID NO:9283, SEQ ID NO: 9308, SEQ ID NO: 9309, SEQ ID NO:9310, or SEQ ID NO:9311 and retains fusogenic activity in conjunction with a Henipavirus G protein (e.g., NiV-G or HeV-G). In some embodiments, the biologically active portion has an amino acid sequence having at least at or about 80%, at least at or about 85%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9258, SEQ ID NO:9259, SEQ ID NO:9274, SEQ ID NO:9281, SEQ ID NO:9282, SEQ ID NO:9283, SEQ ID NO:9308, SEQ ID NO:9309, SEQ ID NO:9310, or SEQ ID NO: 9311 and retains fusogenic activity in conjunction with a Henipavirus G protein (e.g., NiV-G or HeV-G).

Reference to retaining fusogenic activity includes activity (in conjunction with a Henipavirus G protein) that is at or about 10% to at or about 150% or more of the level or degree of binding of the corresponding wild-type F protein, such as set forth in SEQ ID NO:9258, SEQ ID NO:9259, SEQ ID NO:9274, SEQ ID NO:9281, SEQ ID NO: 9282, SEQ ID NO: 9283, SEQ ID NO:9308, SEQ ID NO:9309, SEQ ID NO:9310, or SEQ ID NO:9311, such as at least or at least about 10% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 15% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 20% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 25% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 30% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 35% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 40% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 45% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 50% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 55% of the level or degree of fusogenic activity of the corresponding wild-type f protein, such as at least or at least about 60% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 65% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 70% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 75% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 80% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 85% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 90% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 95% of the level or degree of fusogenic activity of the corresponding wild-type F protein, such as at least or at least about 100% of the level or degree of fusogenic activity of the corresponding wild-type F protein, or such as at least or at least about 120% of the level or degree of fusogenic activity of the corresponding wild-type F protein.

In some embodiments, the F protein is a mutant F protein that is a functionally active fragment or a biologically active portion containing one or more amino acid mutations, such as one or more amino acid insertions, deletions, substitutions, or truncations. In some embodiments, the mutations described herein relate to amino acid insertions, deletions, substitutions, or truncations of amino acids compared to a reference F protein sequence. In some embodiments, the reference F protein sequence is the wild-type sequence of an F protein or a biologically active portion thereof. In some embodiments, the mutant F protein or the biologically active portion thereof is a mutant of a wild-type Hendra (Hev) virus F protein, a Nipah (NiV) virus F-protein, a Cedar (CedPV) virus F protein, a Mojiang virus F protein, or a bat Paramyxovirus F protein. In some embodiments, the wild-type F protein is encoded by a sequence of nucleotides that encodes any one of SEQ ID NO: 592, 593, 608, 614-616, or 641-644.

In some embodiments, the mutant F protein is a biologically active portion of a wild-type F protein that is an N-terminally and/or C-terminally truncated fragment. In some embodiments, the mutant F protein or the biologically active portion of a wild-type F protein thereof comprises one or more amino acid substitutions. In some embodiments, the mutations described herein improve transduction efficiency. In some embodiments, the mutations described herein increase fusogenic capacity. Exemplary mutations include any as described, see e.g. Khetawat and Broder 2010 Virology Journal 7:312; Witting et al. 2013 Gene Therapy 20:997-1005; published international; patent application No. WO/2013/148327.

In some embodiments, the mutant F protein is a biologically active portion that is truncated and lacks up to 20 contiguous amino acid residues at or near the C-terminus of the wild-type F protein, such as a wild-type F protein encoded by a sequence of nucleotides encoding the F protein set forth in any one of SEQ ID NOS: 592, 593, 608, or 614-616. In some embodiments, the mutant F protein is truncated and lacks up to 19 contiguous amino acids, such as up to 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 contiguous amino acid(s) at the C-terminus of the wild-type F protein.

In some embodiments, the F protein or the functionally active variant or biologically active portion thereof comprises an F1 subunit or a fusogenic portion thereof. In some embodiments, the F1 subunit is a proteolytically cleaved portion of the F0 precursor. In some embodiments, the F0 precursor is inactive. In some embodiments, the cleavage of the F0 precursor forms a disulfide-linked F1+F2 heterodimer. In some embodiments, the cleavage exposes the fusion polypeptide and produces a mature F protein. In some embodiments, the cleavage occurs at or around a single basic residue. In some embodiments, the cleavage occurs at Arginine 109 of NiV-F protein. In some embodiments, cleavage occurs at Lysine 109 of the Hendra virus F protein.

In some embodiments, the F protein is a wild-type Nipah virus F (NiV-F) protein or is a functionally active variant or biologically active portion thereof. In some embodiments, the F₀ precursor is encoded by a sequence of nucleotides encoding the sequence set forth in SEQ ID NO:9258. The encoding nucleic acid can encode a signal polypeptide sequence that has the sequence MVVILDKRCY CNLLILILMI SECSVG (SEQ ID NO:9291) or another signal polypeptide sequence. In some embodiments, the F protein has the sequence set forth in SEQ ID NO:9259. In some examples, the F protein is cleaved into an F1 subunit comprising the sequence set forth in SEQ ID NO:9261 and an F2 subunit comprising the sequence set forth in SEQ ID NO:9260.

In some embodiments, the F protein is a NiV-F protein that is encoded by a sequence of nucleotides encoding the sequence set forth in SEQ ID NO:9258, or is a functionally active variant or biologically active portion thereof that has an amino acid sequence having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9258. In some embodiments, the NiV-F-protein has the sequence of set forth in SEQ ID NO:9259, or is a functionally active variant or a biologically active portion thereof that has an amino acid sequence having at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89%, at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9259. In particular embodiments, the F protein or the functionally active variant or biologically active portion thereof retains the cleavage site cleaved by cathepsin L (e.g., corresponding to the cleavage site between amino acids 109-110 of SEQ ID NO:9258).

In some embodiments, the F protein or the functionally active variant or the biologically active portion thereof includes an F1 subunit that has the sequence set forth in SEQ ID NO:9261, or an amino acid sequence having, at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89% at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9261.

In some embodiments, the F protein or the functionally active variant or biologically active portion thereof includes an F2 subunit that has the sequence set forth in SEQ ID NO: 9260, or an amino acid sequence having, at least at or about 80%, at least at or about 81%, at least at or about 82%, at least at or about 83%, at least at or about 84%, at least at or about 85%, at least at or about 86%, at least at or about 87%, at least at or about 88%, at least at or about 89% at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO: 9260.

In some embodiments, the F protein is a mutant NiV-F protein that is a biologically active portion thereof that is truncated and lacks up to 20 contiguous amino acid residues at or near the C-terminus of the wild-type NiV-F protein (e.g., set forth SEQ ID NO: 9259). In some embodiments, the mutant NiV-F protein comprises an amino acid sequence set forth in SEQ ID NO:9262. In some embodiments, the mutant NiV-F protein has a sequence that has at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9262. In some embodiments, the mutant F protein contains an F1 protein that has the sequence set forth in SEQ ID NO:9263. In some embodiments, the mutant F protein has a sequence that has at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9263.

In some embodiments, the F protein is a mutant NiV-F protein that is a biologically active portion thereof that comprises a 20 amino acid truncation at or near the C-terminus of the wild-type NiV-F protein (SEQ ID NO:9259); and a point mutation on an N-linked glycosylation site. In some embodiments, the mutant NiV-F protein comprises an amino acid sequence set forth in SEQ ID NO:9264. In some embodiments, the mutant NiV-F protein has a sequence that has at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9264.

In some embodiments, the F protein is a mutant NiV-F protein that is a biologically active portion thereof that comprises a 22 amino acid truncation at or near the C-terminus of the wild-type NiV-F protein (SEQ ID NO:9259). In some embodiments, the NiV-F protein comprises an amino acid sequence set forth in SEQ ID NO:9265. In some embodiments, the NiV-F protein has a sequence with at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9265. In particular embodiments, the variant F protein is a mutant Niv-F protein that has the sequence of amino acids set forth in SEQ ID NO:9280. In some embodiments, the NiV-F protein has a sequence with at least at or about 90%, at least at or about 91%, at least at or about 92%, at least at or about 93%, at least at or about 94%, at least at or about 95%, at least at or about 96%, at least at or about 97%, at least at or about 98%, or at least at or about 99% sequence identity to SEQ ID NO:9280.

It has been reported that the henipavirus F proteins from various species exhibit compatibility with G proteins from other species to trigger fusion (Brandel-Tretheway et al. Journal of Virology. 2019. 93(13):e00577-19). In some aspects of the provided lentiviral vector, the F protein is heterologous to the G protein, i.e. the F and G protein or biologically active portions are from different henipavirus species. For example, the G protein is from Hendra virus and the F protein is a NiV-F as described. In other aspects, the F and/or G protein can be a chimeric F and/or G protein containing regions of F and/or G proteins from different species of Henipavirus. In some embodiments, replacing a portion of the F protein with amino acids from a heterologous sequence of Henipavirus results in fusion to the G protein with the heteroglous sequence. (Brandel-Tretheway et al. 2019). In some cases, the chimeric F and/or G protein contains an extracellular domain from one henipavirus species and a transmembrane and/or cytoplasmic domain from a different henipavirus species. For example, the F protein contains an extracellular domain of Hendra virus and a transmembrane/cytoplasmic domain of Nipah virus.

B. Lipid Bilayer

In some embodiments, the targeted lipid particle includes a naturally derived bilayer of amphipathic lipids that encloses a lumen or cavity. In some embodiments, the targeted lipid particle comprises a lipid bilayer as the outermost surface. In some embodiments, the lipid bilayer encloses a lumen. In some embodiments, the lumen is aqueous. In some embodiments, the lumen is in contact with the hydrophilic head groups on the interior of the lipid bilayer. In some embodiments, the lumen is a cytosol. In some embodiments, the cytosol contains cellular components present in a source cell. In some embodiments, the cytosol does not contain cellular components present in a source cell. In some embodiments, the lumen is a cavity. In some embodiments, the cavity contains an aqueous environment. In some embodiments, the cavity does not contain an aqueous environment.

In some aspects, the lipid bilayer is derived from a source cell during a process to produce a lipid-containing particle. In some embodiments, the lipid bilayer includes membrane components of the cell from which the lipid bilayer is produced, e.g., phospholipids, membrane proteins, etc. In some embodiments, the lipid bilayer includes a cytosol that includes components found in the cell from which the lipid bilayer is produced, e.g., solutes, proteins, nucleic acids, etc., but not all of the components of a cell, e.g., it lacks a nucleus. In some embodiments, the lipid bilayer is considered to be exosome-like. The lipid particle may vary in size, and in some instances have a diameter ranging from 30 and 300 nm, such as from 30 and 150 nm, and including from 40 to 100 nm.

In some embodiments, the lipid bilayer is a viral envelope. In some embodiments, the viral envelope is obtained from a source cell. In some embodiments, the viral envelope is obtained from the source cell plasma membrane. In some embodiments, the lipid bilayer is obtained from a membrane other than the plasma membrane of a host cell. In some embodiments, the viral envelope lipid bilayer is embedded with viral proteins, including viral glycoproteins.

In other aspects, the lipid bilayer includes synthetic lipid complex. In some embodiments, the lipid bilayer is a liposome that includes a synthetic lipid complex. In some embodiments, the lipid particle is a vesicular structure characterized by a phospholipid bilayer membrane and an inner aqueous medium. In some embodiments, the lipid bilayer has multiple lipid layers separated by aqueous medium. In some embodiments, the lipid bilayer forms spontaneously when phospholipids are suspended in an excess of aqueous solution. In some examples, the lipid components undergo self-rearrangement before the formation of closed structures and entrap water and dissolved solutes between the lipid bilayers. In some embodiments the lipid bilayer is a fusosome.

In some embodiments, a targeted envelope protein and fusogen, such as any described above including any that are exogenous or overexpressed relative to the source cell, is disposed in the lipid bilayer.

In some embodiments, the targeted lipid particle comprises several different types of lipids. In some embodiments, the lipids are amphipathic lipids. In some embodiments, the amphipathic lipids are phospholipids. In some embodiments, the phospholipids comprise phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine. In some embodiments, the lipids comprise DMPC, DOPC, and DSPC.

In some embodiments, the bilayer is comprised of one or more lipids of the same or different type. In some embodiments, the source cell comprises a cell selected from CHO cells, BHK cells, MDCK cells, C3H 10T1/2 cells, FLY cells, Psi-2 cells, BOSC 23 cells, PA317 cells, WEHI cells, COS cells, BSC 1 cells, BSC 40 cells, BMT 10 cells, VERO cells, W138 cells, MRC5 cells, A549 cells, HT1080 cells, 293 cells, 293T cells, B-50 cells, 3T3 cells, NIH3T3 cells, HepG2 cells, Saos-2 cells, Huh7 cells, Hela cells, W163 cells, 211 cells, and 211A cells.

C. Exogenous Agent

In some embodiments, the targeted lipid particle further comprises an agent that is exogenous relative to the source cell (also referred to herein as a “cargo” or “payload”). In some embodiments, the exogenous agent is a small molecule, a protein, or a nucleic acid (e.g., a DNA, a chromosome (e.g. a human artificial chromosome), an RNA, e.g., an mRNA or miRNA). In some embodiments, the exogenous agent or cargo encodes a cytosolic protein. In some embodiments the exogenous agent or cargo comprises or encodes a membrane protein. In some embodiments, the exogenous agent or cargo comprises a therapeutic agent. In some embodiments, the therapeutic agent is chosen from one or more of a protein, e.g., an enzyme, a transmembrane protein, a receptor, an antibody; a nucleic acid, e.g., DNA, a chromosome (e.g. a human artificial chromosome), RNA, mRNA, siRNA, miRNA; or a small molecule.

In some embodiments, the exogenous agent is present in at least, or no more than, 10, 20, 50, 100, 200, 500, 1,000, 2,000, 5,000, 10,000, 20,000, 50,000, 100,000, 200,000, 500,000, 1,000,000, 5,000,000, 10,000,000, 50,000,000, 100,000,000, 500,000,000, or 1,000,000,000 copies. In some embodiments, the targeted lipid particle has an altered, e.g., increased or decreased level of one or more endogenous molecules, e.g., protein or nucleic acid (e.g., in some embodiments, endogenous relative to the source cell, and in some embodiments, endogenous relative to the target cell), e.g., due to treatment of the source cell, e.g., mammalian source cell with a siRNA or gene editing enzyme. In some embodiments, the endogenous molecule is present in at least, or no more than, 10, 20, 50, 100, 200, 500, 1,000, 2,000, 5,000, 10,000, 20,000, 50,000, 100,000, 200,000, 500,000, 1,000,000, 5,000,000, 10,000,000, 50,000,000, 100,000,000, 500,000,000, or 1,000,000,000 copies. In some embodiments, the endogenous molecule (e.g., an RNA or protein) is present at a concentration of at least 1, 2, 3, 4, 5, 10, 20, 50, 100, 500, 10³, 5.0×10³, 10⁴, 5.0×10⁴, 10⁵, 5.0×10⁵, 10⁶, 5.0×10⁶, 1.0×10⁷, 5.0×10⁷, or 1.0×10⁸, greater than its concentration in the source cell. In some embodiments, the endogenous molecule (e.g., an RNA or protein) is present at a concentration of at least 1, 2, 3, 4, 5, 10, 20, 50, 100, 500, 10³, 5.0×10³, 10⁴, 5.0×10⁴, 10⁵, 5.0×10⁵, 10⁶, 5.0×10⁶, 1.0×10⁷, 5.0×10⁷, or 1.0×10⁸ less than its concentration in the source cell.

In some embodiments, the targeted lipid particle (e.g., targeted viral vector) delivers to a target cell at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the cargo (e.g., a therapeutic agent, e.g., an exogenous therapeutic agent) comprised by the targeted lipid particle. In some embodiments, the targeted lipid particle that fuses with the target cell(s) delivers to the target cell an average of at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the cargo (e.g., a therapeutic agent, e.g., an exogenous therapeutic agent) comprised by the targeted lipid particle that fuses with the target cell(s). In some embodiments, the targeted lipid particle composition delivers to a target tissue at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the cargo (e.g., a therapeutic agent, e.g., an exogenous therapeutic agent) comprised by the targeted lipid particle composition.

In some embodiments, the exogenous agent or cargo is not expressed naturally in the cell from which the targeted lipid particle is derived. In some embodiments, the exogenous agent or cargo is expressed naturally in the cell from which the viral vector is derived. In some embodiments, the exogenous agent or cargo is loaded into the targeted lipid particle via expression in the cell from which the viral vector is derived (e.g. expression from DNA or mRNA introduced via transfection, transduction, or electroporation). In some embodiments, the exogenous agent or cargo is expressed from DNA integrated into the genome or maintained episomally. In some embodiments, expression of the exogenous agent or cargo is constitutive. In some embodiments, expression of the exogenous agent or cargo is induced. In some embodiments, expression of the exogenous agent or cargo is induced immediately prior to generating the targeted lipid particle. In some embodiments, expression of the exogenous agent or cargo is induced at the same time as expression of the fusogen.

In some embodiments, the exogenous agent or cargo is loaded into the viral vector via electroporation into the viral vector itself or into the cell from which the viral vector is derived. In some embodiments, the exogenous agent or cargo is loaded into the viral vector via transfection (e.g., of a DNA or mRNA encoding the cargo) into the viral vector itself or into the cell from which the viral vector is derived.

In some embodiments, the exogenous agent or cargo includes one or more nucleic acid sequences, one or more amino acid sequences, a combination of nucleic acid sequences and/or amino acid sequences, one or more organelles, and any combination thereof. In some embodiments, the exogenous agent or cargo includes one or more cellular components. In some embodiments, the exogenous agent or cargo includes one or more cytosolic and/or nuclear components.

In some embodiments, the exogenous agent or cargo includes a nucleic acid, e.g., DNA, nDNA (nuclear DNA), mtDNA (mitochondrial DNA), protein coding DNA, gene, operon, chromosome, genome, transposon, retrotransposon, viral genome, intron, exon, modified DNA, mRNA (messenger RNA), tRNA (transfer RNA), modified RNA, microRNA, siRNA (small interfering RNA), tmRNA (transfer messenger RNA), rRNA (ribosomal RNA), mtRNA (mitochondrial RNA), snRNA (small nuclear RNA), small nucleolar RNA (snoRNA), SmY RNA (mRNA trans-splicing RNA), gRNA (guide RNA), TERC (telomerase RNA component), aRNA (antisense RNA), cis-NAT (Cis-natural antisense transcript), CRISPR RNA (crRNA), lncRNA (long noncoding RNA), piRNA (piwi-interacting RNA), shRNA (short hairpin RNA), tasiRNA (trans-acting siRNA), eRNA (enhancer RNA), satellite RNA, pcRNA (protein coding RNA), dsRNA (double stranded RNA), RNAi (interfering RNA), circRNA (circular RNA), reprogramming RNAs, aptamers, and any combination thereof. In some embodiments, the nucleic acid is a wild-type nucleic acid. In some embodiments, the nucleic acid is a mutant nucleic acid. In some embodiments the nucleic acid is a fusion or chimera of multiple nucleic acid sequences.

In some embodiments, the exogenous agent or cargo includes a nucleic acid. For example, the exogenous agent or cargo may comprise RNA to enhance expression of an endogenous protein, or a siRNA or miRNA that inhibits protein expression of an endogenous protein. For example, the endogenous protein may modulate structure or function in the target cells. In some embodiments, the cargo includes a nucleic acid encoding an engineered protein that modulates structure or function in the target cells. In some embodiments, the exogenous agent or cargo is a nucleic acid that targets a transcriptional activator that modulate structure or function in the target cells.

In some embodiments, the exogenous agent or cargo includes a polypeptide, e.g., enzymes, structural proteins, signaling proteins, regulatory proteins, transport proteins, sensory proteins, motor proteins, defense proteins, storage proteins, transcription factors, antibodies, cytokines, hormones, catabolic proteins, anabolic proteins, proteolytic proteins, metabolic proteins, kinases, transferases, hydrolases, lyases, isomerases, ligases, enzyme modulator proteins, protein binding polypeptides, lipid binding proteins, membrane fusion proteins, cell differentiation proteins, epigenetic proteins, cell death proteins, nuclear transport proteins, nucleic acid binding proteins, reprogramming proteins, DNA editing proteins, DNA repair proteins, DNA recombination proteins, transposase proteins, DNA integration proteins, targeted endonucleases (e.g. Zinc-finger nucleases, transcription-activator-like nucleases (TALENs), cas9 and homologs thereof), recombinases, and any combination thereof. In some embodiments the protein targets a protein in the cell for degradation. In some embodiments the protein targets a protein in the cell for degradation by localizing the protein to the proteasome. In some embodiments, the protein is a wild-type protein. In some embodiments, the protein is a mutant protein. In some embodiments the protein is a fusion or chimeric protein.

In some embodiments, the exogenous agent or cargo includes a small molecule, e.g., ions (e.g. Ca²⁺, C1−, Fe²⁺), carbohydrates, lipids, reactive oxygen species, reactive nitrogen species, isoprenoids, signaling molecules, heme, peptide cofactors, electron accepting compounds, electron donating compounds, metabolites, ligands, and any combination thereof. In some embodiments the small molecule is a pharmaceutical that interacts with a target in the cell. In some embodiments the small molecule targets a protein in the cell for degradation. In some embodiments the small molecule targets a protein in the cell for degradation by localizing the protein to the proteasome. In some embodiments that small molecule is a proteolysis targeting chimera molecule (PROTAC).

In some embodiments, the exogenous agent or cargo includes a mixture of proteins, nucleic acids, or metabolites, e.g., multiple amino acids, multiple nucleic acids, multiple small molecules; combinations of nucleic acids, amino acids, and small molecules; ribonucleoprotein complexes (e.g. Cas9-gRNA complex); multiple transcription factors, multiple epigenetic factors, reprogramming factors (e.g. Oct4, Sox2, cMyc, and Klf4); multiple regulatory RNAs; and any combination thereof.

In some embodiments, the exogenous agent or cargo includes one or more organelles, e.g., chondriosomes, mitochondria, lysosomes, nucleus, cell membrane, cytoplasm, endoplasmic reticulum, ribosomes, vacuoles, endosomes, spliceosomes, polymerases, capsids, acrosome, autophagosome, centriole, glycosome, glyoxysome, hydrogenosome, melanosome, mitosome, myofibril, cnidocyte, peroxisome, proteasome, vesicle, stress granule, networks of organelles, and any combination thereof.

In some embodiments, the exogenous agent encodes a therapeutic agent or a diagnostic agent. In some embodiments, the therapeutic agent is a chimeric antigen receptor (CAR) or T-cell receptor (TCR). In some embodiments, the CAR targets a tumor antigen selected from CD19, CD20, CD22, or BCMA. In another embodiment, the CAR is engineered to comprise an intracellular signaling domain of the T cell antigen receptor complex zeta chain (e.g., CD3 zeta). In a preferred embodiment, the intracellular domain is selected from a CD137 (4-1BB) signaling domain, a CD28 signaling domain, and a CD3zeta signaling domain.

D. Methods of Generating Targeted Lipid Particles Derived from Virus

Provided herein are targeted lipid particles that are derived from virus, such as viral particles or virus-like particles, including those derived from retroviruses or lentiviruses. In some embodiments, the targeted lipid particle's bilayer of amphipathic lipids is or comprises the viral envelope. In some embodiments, the targeted lipid particle's bilayer of amphipathic lipids is or comprises lipids derived from a producer cell. In some embodiments, the viral envelope comprises a fusogen, e.g., a fusogen that is endogenous to the virus or a pseudotyped fusogen. In some embodiments, the targeted lipid particle's lumen or cavity comprises a viral nucleic acid, e.g., a retroviral nucleic acid, e.g., a lentiviral nucleic acid. In some embodiments, the viral nucleic acid is a viral genome. In some embodiments, the targeted lipid particle further comprises one or more viral non-structural proteins, e.g., in its cavity or lumen. In some embodiments, the targeted lipid particle is or comprises a virus-like particle (VLP). In some embodiments, the VLP does not comprise an envelope. In some embodiments, the VLP comprises an envelope.

In some embodiments, the viral particle or virus-like particle, such as a retrovirus or retrovirus-like particle, comprises one or more of a Gag polyprotein, polymerase (e.g., Pol), integrase (IN, e.g., a functional or non-functional variant), protease (PR), and a fusogen. In some embodiments, the targeted lipid particle further comprises Rev. In some embodiments, one or more of the aforesaid proteins are encoded in the retroviral genome, and in some embodiments, one or more of the aforesaid proteins are provided in trans, e.g., by a helper cell, helper virus, or helper plasmid. In some embodiments, the targeted lipid particle nucleic acid (e.g., retroviral nucleic acid) comprises one or more of the following nucleic acid sequences: 5′ LTR (e.g., comprising U5 and lacking a functional U3 domain), Psi packaging element (Psi), Central polypurine tract (cPPT) Promoter operatively linked to the payload gene, payload gene (optionally comprising an intron before the open reading frame), Poly A tail sequence, WPRE, and 3′ LTR (e.g., comprising U5 and lacking a functional U3). In some embodiments the targeted lipid particle nucleic acid further comprises one or more insulator elements. In some embodiments, the recognition sites are situated between the poly A tail sequence and the WPRE.

In some embodiments, the targeted lipid particle comprises supramolecular complexes formed by viral proteins that self-assemble into capsids. In some embodiments, the targeted lipid particle is a viral particle or virus-like particle derived from viral capsids. In some embodiments, the targeted lipid particle is a viral particle or virus-like particle derived from viral nucleocapsids. In some embodiments, the targeted lipid particle comprises nucleocapsid-derived proteins that retain the property of packaging nucleic acids. In some embodiments, the viral particles or virus-like particles comprise only viral structural glycoproteins. In some embodiments, the targeted lipid particle does not contain a viral genome.

In some embodiments, the targeted lipid particle packages nucleic acids from host cells during the expression process. In some embodiments, the nucleic acids do not encode any genes involved in virus replication. In particular embodiments, the targeted lipid particle is a virus-like particle, e.g. retrovirus-like particle such as a lentivirus-like particle, that is replication defective.

In some cases, the targeted lipid particle is a viral particle that is morphologically indistinguishable from the wild type infectious virus. In some embodiments, the viral particle presents the entire viral proteome as an antigen. In some embodiments, the viral particle presents only a portion of the proteome as an antigen.

In some embodiments, the viral particle or virus-like particle is produced utilizing proteins (e.g., envelope proteins) from a virus within the Paramyxoviridae family. In some embodiments, the Paramyxoviridae family comprises members within the Henipavirus genus. In some embodiments, the Henipavirus is or comprises a Hendra (HeV) or a Nipah (NiV) virus. In particular embodiments, the viral particles or virus-like particles incorporate a targeted envelope protein and fusogen.

In some embodiments, viral particles or virus-like particles is produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast, and plant cells.

Suitable cell lines which can be used include, for example, CHO cells, BHK cells, MDCK cells, C3H 10T1/2 cells, FLY cells, Psi-2 cells, BOSC 23 cells, PA317 cells, WEHI cells, COS cells, BSC 1 cells, BSC 40 cells, BMT 10 cells, VERO cells, W138 cells, MRC5 cells, A549 cells, HT1080 cells, 293 cells, 293T cells, B-50 cells, 3T3 cells, NIH3T3 cells, HepG2 cells, Saos-2 cells, Huh7 cells, Hela cells, W163 cells, 211 cells, 211A cells, and cyno and Macaca nemestrina cell lines. In embodiments, the packaging cells are 293 cells, 293T cells, or A549 cells.

In some embodiments, a source cell line includes a cell line which is capable of producing recombinant retroviral particles, comprising a producer cell line and a transfer vector construct comprising a packaging signal. Methods of preparing viral stock solutions are illustrated by, e.g., Y. Soneoka et al. (1995) Nucl. Acids Res. 23:628-633, and N. R. Landau et al. (1992) J. Virol. 66:5110-5113, which are incorporated herein by reference.

In some embodiments, the assembly of a viral particle or virus-like particle is initiated by binding of the core protein to a unique encapsidation sequence within the viral genome (e.g. UTR with stem-loop structure). In some embodiments, the interaction of the core with the encapsidation sequence facilitates oligomerization.

In some embodiments, the targeted lipid particle is a virus-like particle which comprises a sequence that is devoid of or lacking viral RNA. In some embodiments, such particles are the result of removing or eliminating the viral RNA from the sequence. In some embodiments, this is achieved by using an endogenous packaging signal binding site on Gag. In some embodiments, the endogenous packaging signal binding site is on Pol. In some embodiments, the RNA which is to be delivered will contain a cognate packaging signal. In some embodiments, a heterologous binding domain (which is heterologous to Gag) located on the RNA to be delivered, and a cognate binding site located on Gag or Pol, is used to ensure packaging of the RNA to be delivered. In some embodiments, the heterologous sequence is non-viral or it could be viral, in which case it is derived from the same virus or a different virus. In some embodiments, the vector particles could be used to deliver therapeutic RNA, in which case functional integrase and/or reverse transcriptase is not required. In some embodiments, the vector particles could also be used to deliver a therapeutic gene of interest, in which case Pol is typically included. In some embodiments, the retroviral nucleic acid comprises one or more of (e.g., all of): a 5′ promoter (e.g., to control expression of the entire packaged RNA), a 5′ LTR (e.g., that includes R (polyadenylation tail signal) and/or U5 which includes a primer activation signal), a primer binding site, a Psi packaging signal, a RRE element for nuclear export, a promoter directly upstream of the transgene to control transgene expression, a transgene (or other exogenous agent element), a polypurine tract, and a 3′ LTR (e.g., that includes a mutated U3, a R, and U5). In some embodiments, the retroviral nucleic acid further comprises one or more of a cPPT, a WPRE, and/or an insulator element.

A retrovirus typically replicates by reverse transcription of its genomic RNA into a linear double-stranded DNA copy and subsequently covalently integrates its genomic DNA into a host genome. Illustrative retroviruses suitable for use in particular embodiments, include, but are not limited to: Moloney murine leukemia virus (M-MuLV), Moloney murine sarcoma virus (MOMSV), Harvey murine sarcoma virus (HaMuSV), murine mammary tumor virus (MuMTV), gibbon ape leukemia virus (GaLV), feline leukemia virus (FLV), spumavirus, Friend murine leukemia virus, Murine Stem Cell Virus (MSCV), Rous Sarcoma Virus (RSV), and other lentiviruses.

In some embodiments the retrovirus is a Gammaretrovirus. In some embodiments the retrovirus is an Epsilonretrovirus. In some embodiments the retrovirus is an Alpharetrovirus. In some embodiments the retrovirus is a Betaretrovirus. In some embodiments the retrovirus is a Deltaretrovirus. In some embodiments the retrovirus is a Lentivirus. In some embodiments the retrovirus is a Spumaretrovirus. In some embodiments the retrovirus is an endogenous retrovirus.

Illustrative lentiviruses include, but are not limited to: HIV (human immunodeficiency virus; including HIV type 1, and HIV type 2); visna-maedi virus (VMV) virus; the caprine arthritis-encephalitis virus (CAEV); equine infectious anemia virus (EIAV); feline immunodeficiency virus (FIV); bovine immune deficiency virus (BIV); and simian immunodeficiency virus (SIV). In some embodiments, HIV based vector backbones (i.e., HIV cis-acting sequence elements) are used.

In some embodiments, a vector herein is a nucleic acid molecule capable transferring or transporting another nucleic acid molecule. The transferred nucleic acid is generally linked to, e.g., inserted into, the vector nucleic acid molecule. A vector may include sequences that direct autonomous replication in a cell, or may include sequences sufficient to allow integration into host cell DNA. Useful vectors include, for example, plasmids (e.g., DNA plasmids or RNA plasmids), transposons, cosmids, bacterial artificial chromosomes, and viral vectors. Useful viral vectors include, e.g., replication defective retroviruses and lentiviruses.

In some embodiments, a viral vector comprises a nucleic acid molecule (e.g., a transfer plasmid) that includes virus-derived nucleic acid elements that typically facilitate transfer of the nucleic acid molecule or integration into the genome of a cell or to a viral particle that mediates nucleic acid transfer. Viral particles will typically include various viral components and sometimes also host cell components in addition to nucleic acid(s). In some embodiments, a viral vector comprises e.g., a virus or viral particle capable of transferring a nucleic acid into a cell, or the transferred nucleic acid (e.g., as naked DNA). In some embodiments, a viral vectors and transfer plasmids comprise structural and/or functional genetic elements that are primarily derived from a virus. A retroviral vector can comprise a viral vector or plasmid containing structural and functional genetic elements, or portions thereof, that are primarily derived from a retrovirus. A lentiviral vector can comprise a viral vector or plasmid containing structural and functional genetic elements, or portions thereof, including LTRs that are primarily derived from a lentivirus.

In embodiments, a lentiviral vector (e.g., lentiviral expression vector) comprises a lentiviral transfer plasmid (e.g., as naked DNA) or an infectious lentiviral particle. With respect to elements such as cloning sites, promoters, regulatory elements, heterologous nucleic acids, etc., it is to be understood that the sequences of these elements can be present in RNA form in lentiviral particles and can be present in DNA form in DNA plasmids.

In some embodiments, the viral vector further comprises a vector-surface targeting moiety which specifically binds to a target ligand. In some embodiments, the vector-surface targeting moiety is a polypeptide. In some embodiments, a nucleic acid encoding the Paramyxovirus envelope protein (e.g. G protein) is modified with a targeting moiety to specifically bind to a target molecule on a target cells. In some embodiments, the targeting moiety is any targeting protein, including but not necessarily limited to antibodies and antigen binding fragments thereof.

In some embodiments, in the vectors described herein at least part of one or more protein coding regions that contribute to or are essential for replication are absent compared to the corresponding wild-type virus. In some embodiments, the viral vector is replication-defective. In some embodiments, the vector is capable of transducing a target non-dividing host cell and/or integrating its genome into a host genome.

In some embodiments, different cells differ in their usage of particular codons. In some embodiments, this codon bias corresponds to a bias in the relative abundance of particular tRNAs in the cell type. In some embodiments, by altering the codons in the sequence so that they are tailored to match with the relative abundance of corresponding tRNAs, it is possible to increase expression. In some embodiments, it is possible to decrease expression by deliberately choosing codons for which the corresponding tRNAs are known to be rare in the particular cell type. In some embodiments, an additional degree of translational control is available. An additional description of codon optimization is found, e.g., in WO 99/41397, which is herein incorporated by reference in its entirety.

Conventional techniques for generating retrovirus vectors (and, in particular, lentivirus vectors) with or without the use of packaging/helper vectors are known to those skilled in the art and may be used to generate targeted lipid particles according to the present disclosure. (See, e.g., Derse and Newbold 1993 Virology 194:530-6; Maury et al. 1994 Virology 200:632-42; Wanisch et al. 2009. Mol Ther. 1798:1316-1332; Martarano et al. 1994 J. Virol. 68:3102-11; Naldini et al., (1996a, 1996b, and 1998); Zufferey et al., 1999, J. Virol., 73:2886; Huang et al., Mol. Cell. Biol., 5:3864; Liu et al., 1995, Genes Dev., 9:1766; Cullen et al., 1991. J. Virol. 65:1053; and Cullen et al., 1991. Cell 58:423; Dull et al., 1998, U.S. Pat. Nos. 6,013,516; and 5,994,136; PCT patent applications WO 99/15683, WO 98/17815, WO 99/32646, and WO 01/79518). Conventional techniques relating to packaging vectors and producer cells known in the art may also be used according to the present disclosure. (See, e.g., Yao et al, 1998; Jones et al, 2005.)

Provided herein are targeted lipid particles that comprise a naturally derived membrane. In some embodiments, the naturally derived membrane comprises membrane vesicles prepared from cells or tissues. In some embodiments, the targeted lipid particle comprises a vesicle that is obtainable from a cell. In some embodiments, the targeted lipid particle comprises a microvesicle, an exosome, a membrane enclosed body, an apoptotic body (from apoptotic cells), a particle (which may be derived from e.g. platelets), an ectosome (derivable from, e.g., neutrophiles and monocytes in serum), a prostatosome (obtainable from prostate cancer cells), or a cardiosome (derivable from cardiac cells).

In some embodiments, the source cell is an endothelial cell, a fibroblast, a blood cell (e.g., a macrophage, a neutrophil, a granulocyte, a leukocyte), a stem cell (e.g., a mesenchymal stem cell, an umbilical cord stem cell, bone marrow stem cell, a hematopoietic stem cell, an induced pluripotent stem cell e.g., an induced pluripotent stem cell derived from a subject's cells), an embryonic stem cell (e.g., a stem cell from embryonic yolk sac, placenta, umbilical cord, fetal skin, adolescent skin, blood, bone marrow, adipose tissue, erythropoietic tissue, hematopoietic tissue), a myoblast, a parenchymal cell (e.g., hepatocyte), an alveolar cell, a neuron (e.g., a retinal neuronal cell), a precursor cell (e.g., a retinal precursor cell, a myeloblast, myeloid precursor cells, a thymocyte, a meiocyte, a megakaryoblast, a promegakaryoblast, a melanoblast, a lymphoblast, a bone marrow precursor cell, a normoblast, or an angioblast), a progenitor cell (e.g., a cardiac progenitor cell, a satellite cell, a radial glial cell, a bone marrow stromal cell, a pancreatic progenitor cell, an endothelial progenitor cell, a blast cell), or an immortalized cell (e.g., HeEa, HEK293, HFF-I, MRC-5, WI-38, IMR 90, IMR 91, PER.C6, HT-1080, or BJ cell). In some embodiments, the source cell is other than a 293 cell, HEK cell, human endothelial cell, or a human epithelial cell, monocyte, macrophage, dendritic cell, or stem cell.

In some embodiments, the targeted lipid particle has a density of <1, 1-1.1, 1.05-1.15, 1.1-1.2, 1.15-1.25, 1.2-1.3, 1.25-1.35, or >1.35 g/ml. In some embodiments, the targeted lipid particle composition comprises less than 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, or 10% source cells by protein mass, or less than 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, or 10% of cells having a functional nucleus.

In embodiments, the targeted lipid particle has a size, or the population of targeted lipid particles have an average size, that is less than about 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, of that of the source cell.

In some embodiments the targeted lipid particle comprises an extracellular vesicle, e.g., a cell-derived vesicle comprising a membrane that encloses an internal space and has a smaller diameter than the cell from which it is derived. In embodiments the extracellular vesicle has a diameter from 20 nm to 1000 nm. In embodiments the targeted lipid particle comprises an apoptotic body, a fragment of a cell, a vesicle derived from a cell by direct or indirect manipulation, a vesiculated organelle, and a vesicle produced by a living cell (e.g., by direct plasma membrane budding or fusion of the late endosome with the plasma membrane). In embodiments the extracellular vesicle is derived from a living or dead organism, explanted tissues or organs, or cultured cells.

In embodiments, the targeted lipid particle comprises a nanovesicle, e.g., a cell-derived small (e.g., from 20 to 250 nm in diameter, or from 30 to 150 nm in diameter) vesicle comprising a membrane that encloses an internal space, and which is generated from said cell by direct or indirect manipulation. The production of nanovesicles can, in some instances, result in the destruction of the source cell. The nanovesicle may comprise a lipid or fatty acid and a polypeptide.

In embodiments, the targeted lipid particle comprises an exosome. In embodiments, the exosome is a cell-derived small (e.g., from 20 to 300 nm in diameter, or from 40 to 200 nm in diameter) vesicle comprising a membrane that encloses an internal space, and which is generated from said cell by direct plasma membrane budding or by fusion of the late endosome with the plasma membrane. In embodiments, production of exosomes does not result in the destruction of the source cell. In embodiments, the exosome comprises a lipid or fatty acid and a polypeptide.

In some embodiments, the targeted lipid particle is derived from a source cell with a genetic modification which results in increased expression of an immunomodulatory agent. In some embodiments, the immunosuppressive agent is on an exterior surface of the cell. In some embodiments, the immunosuppressive agent is incorporated into the exterior surface of the targeted lipid particle. In some embodiments, the targeted lipid particle comprises an immunomodulatory agent attached to the surface of the solid particle by a covalent or non-covalent bond.

A. Generation of Cell-Derived Particles

In some embodiments, targeted lipid particles are generated by inducing budding of an exosome, microvesicle, membrane vesicle, extracellular membrane vesicle, plasma membrane vesicle, giant plasma membrane vesicle, apoptotic body, mitoparticle, pyrenocyte, lysosome, or other membrane enclosed vesicle.

In some embodiments, targeted lipid particles are generated by inducing cell enucleation. Enucleation may be performed using assays such as genetic, chemical (e.g., using Actinomycin D, see Bayona-Bafaluy et al., “A chemical enucleation method for the transfer of mitochondrial DNA to p° cells” Nucleic Acids Res. 2003 Aug. 15; 31(16):e98), or mechanical methods (e.g., squeezing or aspiration, see Lee et al., “A comparative study on the efficiency of two enucleation methods in pig somatic cell nuclear transfer: effects of the squeezing and the aspiration methods.” Anim Biotechnol. 2008; 19(2):71-9), or combinations thereof.

In some embodiments, the targeted lipid particles are generated by inducing cell fragmentation. In some embodiments, cell fragmentation is performed using the following methods, including, but not limited to: chemical methods, mechanical methods (e.g., centrifugation (e.g., ultracentrifugation, or density centrifugation), freeze-thaw, or sonication), or combinations thereof.

In some embodiments, the targeted lipid particle is a microvesicle. In some embodiments the microvesicle has a diameter of about 100 nm to about 2000 nm. In some embodiments, a targeted lipid particle comprises a cell ghost. In some embodiments, a vesicle is a plasma membrane vesicle, e.g., a giant plasma membrane vesicle.

In some embodiments, a characteristic of a targeted lipid particle is described by comparison to a reference cell. In embodiments, the reference cell is the source cell. In embodiments, the reference cell is a HeLa, HEK293, HFF-1, MRC-5, WI-38, IMR 90, IMR 91, PER.C6, HT-1080, or BJ cell. In some embodiments, for example when the source cell used to make the targeted lipid particle is not available for testing after the targeted lipid particle is made, a characteristic of a population of targeted lipid particle is described by comparison to a population of reference cells, e.g., a population of source cells, or a population of HeLa, HEK293, HFF-1, MRC-5, WI-38, IMR 90, IMR 91, PER.C6, HT-1080, or BJ cells.

Pharmaceutical Compositions

The present disclosure also provides, in some aspects, a pharmaceutical composition comprising the targeted lipid particle (e.g., targeted viral vectors) composition described herein and a pharmaceutically acceptable carrier. The pharmaceutical compositions can include any of the described targeted lipid particles.

In some embodiments, the targeted lipid particle meets a pharmaceutical or good manufacturing practices (GMP) standard. In some embodiments, the targeted lipid particle is made according to good manufacturing practices (GMP). In some embodiments, the targeted lipid particle has a pathogen level below a predetermined reference value, e.g., is substantially free of pathogens. In some embodiments, the targeted lipid particle has a contaminant level below a predetermined reference value, e.g., is substantially free of contaminants. In some embodiments, the targeted lipid particle has low immunogenicity.

In some embodiments, provided herein are the use of pharmaceutical compositions to practice the methods of the disclosure. Such a pharmaceutical composition may comprise at least one targeted lipid particle of the disclosure in a form suitable for administration to a subject, or the pharmaceutical composition may comprise at least one targeted lipid particle of the disclosure and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these.

In some embodiments, the relative amounts of the targeted lipid particle, the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the disclosure will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. In some embodiments, the composition comprises from 0.1% to 100% (w/w) of the targeted lipid particles of the disclosure.

In some embodiments, pharmaceutical compositions that are useful in the methods of the disclosure are suitably developed for intravenous, intratumoral, oral, rectal, vaginal, parenteral, topical, pulmonary, intranasal, buccal, ophthalmic, or another route of administration. In some embodiments, a composition useful within the methods of the disclosure are directly administered to the skin, vagina or any other tissue of a mammal. In some embodiments, formulations include liposomal preparations, resealed erythrocytes containing the targeted lipid particles of the disclosure, and immunologically based formulations. In some embodiments, the route(s) of administration will be readily apparent to the skilled artisan and will depend upon any number of factors including the type and severity of the disease being treated, the type and age of the veterinary or human subject being treated, and the like.

In some embodiments, formulations of the pharmaceutical compositions described herein are prepared by any method known or hereafter developed in the art of pharmacology. In some embodiments, preparatory methods include the step of bringing the targeted lipid particles of the disclosure into association with a carrier or one or more other accessory ingredients, and then, if necessary or desirable, shaping or packaging the product into a desired single- or multi-dose unit.

In some embodiments, a “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the targeted lipid particles of the disclosure. In some embodiments, the amount is generally equal to the dosage that would be administered to a subject or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage. In some embodiments, the unit dosage form is for a single daily dose or one of multiple daily doses (e.g., about 1 to 4 or more times per day). In some embodiments, when multiple daily doses are used, the unit dosage form is the same or different for each dose.

In some embodiments, although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions that are suitable for ethical administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. In some embodiments, modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist may design and perform such modification with merely ordinary, if any, experimentation. In some embodiments, subjects to which administration of the pharmaceutical compositions of the disclosure is contemplated include humans and other primates, mammals including commercially relevant mammals such as cattle, pigs, horses, sheep, cats, and dogs.

In some of any embodiments, the compositions of the disclosure are formulated using one or more pharmaceutically acceptable excipients or carriers. In some embodiments, the pharmaceutical compositions of the disclosure comprise a therapeutically effective amount of a targeted lipid particle of the disclosure and a pharmaceutically acceptable carrier. In some embodiments, pharmaceutically acceptable carriers that are useful, include, but are not limited to, glycerol, water, saline, ethanol, and other pharmaceutically acceptable salt solutions such as phosphates and salts of organic acids. Examples of these and other pharmaceutically acceptable carriers are described in Remington's Pharmaceutical Sciences (1991, Mack Publication Co., New Jersey).

In some embodiments, the carrier is a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. In some embodiments, the proper fluidity is maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. In some embodiments, prevention of the action of microorganisms is achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In some embodiments, it is preferable to include isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, in the composition. In some embodiments, prolonged absorption of the injectable compositions is brought about by including in the composition an agent that delays absorption, for example, aluminum monostearate or gelatin. In some embodiments, the pharmaceutically acceptable carrier is not DMSO alone.

In some embodiments, formulations are employed in admixtures with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for oral, vaginal, parenteral, nasal, intravenous, subcutaneous, enteral, or any other suitable mode of administration, known to the art. In some embodiments, the pharmaceutical preparations are sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, flavoring, and/or aromatic substances and the like. In some embodiments, pharmaceutical preparations are also combined with other active agents, e.g., other analgesic agents.

In some embodiments, “additional ingredients” include, but are not limited to, one or more of the following: excipients; surface active agents; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; sweetening agents; flavoring agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, demulcents; buffers; salts; thickening agents; fillers; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizing agents; and pharmaceutically acceptable polymeric or hydrophobic materials. In some embodiments, “additional ingredients” that are included in the pharmaceutical compositions of the disclosure are known in the art and described, for example in Genaro, ed. (1985, Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa.), which is incorporated herein by reference.

In some embodiments, the composition of the disclosure comprises a preservative from about 0.005% to 2.0% by total weight of the composition. In some embodiments, the preservative is used to prevent spoilage in the case of exposure to contaminants in the environment. In some embodiments, examples of preservatives useful in accordance with the disclosure included but are not limited to those selected from the group consisting of benzyl alcohol, sorbic acid, parabens, imidurea and combinations thereof. In some embodiments, a particularly preferred preservative is a combination of about 0.5% to 2.0% benzyl alcohol and 0.05% to 0.5% sorbic acid.

In some embodiments, liquid suspensions are prepared using conventional methods to achieve suspension of the targeted lipid particles of the disclosure in an aqueous or oily vehicle. In some embodiments, aqueous vehicles include, for example, water, and isotonic saline. In some embodiments, oily vehicles include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. In some embodiments, liquid suspensions further comprise one or more additional ingredients including, but not limited to, suspending agents, dispersing or wetting agents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents, and sweetening agents. In some embodiments, oily suspensions further comprise a thickening agent. In some embodiments, suspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose. In some embodiments, dispersing or wetting agents include, but are not limited to, naturally-occurring phosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, with a long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or with a partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylene sorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to, lecithin, and acacia. Known preservatives include, but are not limited to, methyl, ethyl, or n-propyl-para-hydroxybenzoates, ascorbic acid, and sorbic acid. Known sweetening agents include, for example, glycerol, propylene glycol, sorbitol, sucrose, and saccharin. Known thickening agents for oily suspensions include, for example, beeswax, hard paraffin, and cetyl alcohol.

In some embodiments, liquid solutions of the targeted lipid particles of the disclosure in aqueous or oily solvents are prepared in substantially the same manner as liquid suspensions, the primary difference being that the targeted lipid particles of the disclosure is dissolved, rather than suspended in the solvent. As used herein, an “oily” liquid is one which comprises a carbon-containing liquid molecule and which exhibits a less polar character than water. In some embodiments, liquid solutions of the pharmaceutical composition of the disclosure comprise each of the components described with regard to liquid suspensions, it being understood that suspending agents will not necessarily aid dissolution of the targeted lipid particles of the disclosure in the solvent. In some embodiments, aqueous solvents include, for example, water, and isotonic saline. In some embodiments, oily solvents include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin.

In some embodiments, powdered and granular formulations of a pharmaceutical preparation of the disclosure are prepared using known methods. In some embodiments, formulations are administered directly to a subject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oily suspension or solution by addition of an aqueous or oily vehicle thereto. In some of any embodiments, formulations further comprise one or more of dispersing or wetting agent, a suspending agent, and a preservative. Additional excipients, such as fillers and sweetening, flavoring, or coloring agents, are also included in these formulations.

In some embodiments, a pharmaceutical composition of the disclosure is also prepared, packaged, or sold in the form of oil-in-water emulsion or a water-in-oil emulsion. In some embodiments, the oily phase is a vegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combination of these. In some embodiments, compositions further comprise one or more emulsifying agents such as naturally occurring gums such as gum acacia or gum tragacanth, naturally-occurring phosphatides such as soybean or lecithin phosphatide, esters or partial esters derived from combinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of such partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. In some embodiments, emulsions also contain additional ingredients including, for example, sweetening or flavoring agents.

Methods of Treatment

In some embodiments, the targeted lipid particles (e.g. targeted viral vectors) provided herein, or pharmaceutical compositions thereof as described herein are administered to a subject, e.g. a mammal, e.g. a human. In such embodiments, the subject is at risk of, has a symptom of, or is diagnosed with or identified as having, a particular disease or condition. In some embodiments, the subject has cancer. In some embodiments, the subject has an infectious disease. In some embodiments, the targeted lipid particle contains nucleic acid sequences encoding an exogenous agent for treating the disease or condition in the subject. For example, the exogenous agent is one that targets or is specific for a protein of a neoplastic cells and the targeted lipid particle is administered to a subject for treating a tumor or cancer in the subject. In another example, the exogenous agent is an inflammatory mediator or immune molecule, such as a cytokine, and targeted lipid particle is administered to a subject for treating any condition in which it is desired to modulate (e.g., increase) the immune response, such as a cancer or infectious disease. In some embodiments, the targeted lipid particle is administered in an effective amount or dose to effect treatment of the disease, condition, or disorder. Provided herein are uses of any of the provided targeted lipid particles in such methods and treatments, and in the preparation of a medicament in order to carry out such therapeutic methods. In some embodiments, the methods are carried out by administering the targeted lipid particle or compositions comprising the same, to the subject having, having had, or suspected of having the disease or condition or disorder. In some embodiments, the methods thereby treat the disease or condition or disorder in the subject. Also provided herein are uses of any of the compositions, such as pharmaceutical compositions provided herein, for the treatment of a disease, condition or disorder associated with a particular gene or protein targeted by or provided by the exogenous agent.

In some embodiments, the provided methods or uses involve administration of a pharmaceutical composition comprising oral, inhaled, transdermal or parenteral (including intravenous, intratumoral, intraperitoneal, intramuscular, intracavity, and subcutaneous) administration. In some embodiments, the targeted lipid particle is administered alone or formulated as a pharmaceutical composition. In some embodiments, the targeted lipid particle or compositions described herein are administered to a subject, e.g., a mammal, e.g., a human. In some of any embodiments, the subject is at risk of, has a symptom of, or is diagnosed with or identified as having, a particular disease or condition (e.g., a disease or condition described herein). In some embodiments, the disease is a disease or disorder. In some embodiments, the disease is a B cell malignancy.

In some embodiments, the targeted lipid particles are administered in the form of a unit-dose composition, such as a unit dose oral, parenteral, transdermal, or inhaled composition. In some embodiments, the compositions are prepared by admixture and are adapted for oral, inhaled, transdermal, or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable, and infusible solutions or suspensions, or suppositories or aerosols.

In some embodiments, the regimen of administration affects what constitutes an effective amount. In some embodiments, the therapeutic formulations are administered to the subject either prior to or after a diagnosis of disease. In some embodiments, several divided dosages, as well as staggered dosages are administered daily or sequentially, or the dose is continuously infused, or is a bolus injection. In some embodiments, the dosages of the therapeutic formulations are proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation.

In some embodiments, the administration of the compositions of the present disclosure to a subject, preferably a mammal, more preferably a human, are carried out using known procedures, at dosages and for periods of time effective to prevent or treat disease. In some embodiments, an effective amount of the targeted lipid particle of the disclosure necessary to achieve a therapeutic effect varies according to factors such as the activity of the particular lipid particle employed; the time of administration; the rate of excretion; the duration of the treatment; other drugs, compounds or materials used in combination with the targeted lipid particle of the disclosure; the state of the disease or disorder, age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors well-known in the medical arts. In some embodiments, the dosage regimens are adjusted to provide the optimum therapeutic response. In some embodiments, several divided doses are administered daily or the dose is proportionally reduced as indicated by the exigencies of the therapeutic situation. One of ordinary skill in the art would be able to study the relevant factors and make the determination regarding the effective amount of the therapeutic targeted lipid particle of the disclosure without undue experimentation.

In some embodiments, dosage levels of the targeted lipid particles in the pharmaceutical compositions of this disclosure are varied so as to obtain an amount that is effective to achieve the desired therapeutic response for a particular subject, composition, and mode of administration, without being toxic to the subject.

A medical doctor, e.g., physician or veterinarian, having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. In some embodiments, the physician or veterinarian could start doses of the targeted lipid particles of the disclosure employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.

In some embodiments, the term “container” includes any receptacle for holding the pharmaceutical composition. In some embodiments, the container is the packaging that contains the pharmaceutical composition. In other embodiments, the container is not the packaging that contains the pharmaceutical composition, i.e., the container is a receptacle, such as a box or vial that contains the packaged pharmaceutical composition or unpackaged pharmaceutical composition and the instructions for use of the pharmaceutical composition. It should be understood that the instructions for use of the pharmaceutical composition may be contained on the packaging containing the pharmaceutical composition, and as such the instructions form an increased functional relationship to the packaged product. In some embodiments, instructions contain information pertaining to the pharmaceutical composition's ability to perform its intended function, e.g., treating or preventing a disease in a subject, or delivering an imaging or diagnostic agent to a subject.

In some embodiments, routes of administration of any of the compositions disclosed herein include oral, nasal, rectal, parenteral, sublingual, transdermal, transmucosal (e.g., sublingual, lingual, (trans) buccal, (trans) urethral, vaginal (e.g., trans- and perivaginally), (intra) nasal, and (trans) rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration.

In some of any embodiments, suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration, and the like.

In some embodiments, the targeted lipid particle composition comprising an exogenous agent or cargo, are used to deliver such exogenous agent or cargo to a cell tissue or subject. In some embodiments, delivery of a cargo by administration of a targeted lipid particle composition described herein modify cellular protein expression levels. In certain embodiments, the administered composition directs upregulation (via expression in the cell, delivery in the cell, or induction within the cell) of one or more cargo (e.g., a polypeptide or mRNA) that provide a functional activity which is substantially absent or reduced in the cell in which the polypeptide is delivered. In some embodiments, the missing functional activity is enzymatic, structural, or regulatory in nature. In some embodiments, the administered composition directs up-regulation of one or more proteins that increases (e.g., synergistically) a functional activity which is present but substantially deficient in the cell in which the protein is upregulated. In some of any embodiments disclosed herein, the administered composition directs downregulation of (via expression in the cell, delivery in the cell, or induction within the cell) one or more cargo (e.g., a protein, siRNA, or miRNA) that repress a functional activity which is present or upregulated in the cell in which the protein, siRNA, or miRNA is delivered. In some embodiments, the upregulated functional activity is enzymatic, structural, or regulatory in nature. In some embodiments, the administered composition directs down-regulation of one or more proteins that decreases (e.g., synergistically) a functional activity which is present or upregulated in the cell in which the protein is downregulated. In some embodiments, the administered composition directs upregulation of certain functional activities and downregulation of other functional activities.

In some of any embodiments, the targeted lipid particle composition (e.g., one comprising mitochondria or DNA) mediates an effect on a target cell, and the effect lasts for at least 1, 2, 3, 4, 5, 6, or 7 days, 2, 3, or 4 weeks, or 1, 2, 3, 6, or 12 months. In some embodiments (e.g., wherein the targeted viral vector composition comprises an exogenous protein), the effect lasts for less than 1, 2, 3, 4, 5, 6, or 7 days, 2, 3, or 4 weeks, or 1, 2, 3, 6, or 12 months.

In some of any embodiments, the targeted lipid particle composition described herein is delivered ex-vivo to a cell or tissue, e.g., a human cell or tissue. In embodiments, the composition improves function of a cell or tissue ex-vivo, e.g., improves cell viability, respiration, or other function (e.g., another function described herein).

In some embodiments, the composition is delivered to an ex vivo tissue that is in an injured state (e.g., from trauma, disease, hypoxia, ischemia or other damage).

In some embodiments, the composition is delivered to an ex-vivo transplant (e.g., a tissue explant or tissue for transplantation, e.g., a human vein, a musculoskeletal graft such as bone or tendon, cornea, skin, heart valves, nerves; or an isolated or cultured organ, e.g., an organ to be transplanted into a human, e.g., a human heart, liver, lung, kidney, pancreas, intestine, thymus, eye). In some embodiments, the composition is delivered to the tissue or organ before, during and/or after transplantation.

In some embodiments, the composition is delivered, administered, or contacted with a cell, e.g., a cell preparation. In some embodiments, the cell preparation is a cell therapy preparation (a cell preparation intended for administration to a human subject). In embodiments, the cell preparation comprises cells expressing a T-cell receptor (TCR) or chimeric antigen receptor (CAR), e.g., expressing a recombinant CAR. The cells expressing the CAR may be, e.g., T cells, Natural Killer (NK) cells, cytotoxic T lymphocytes (CTL), regulatory T cells. In embodiments, the cell preparation is a neural stem cell preparation. In embodiments, the cell preparation is a mesenchymal stem cell (MSC) preparation. In embodiments, the cell preparation is a hematopoietic stem cell (HSC) preparation. In embodiments, the cell preparation is an islet cell preparation.

In some embodiments, the viral vector comprising an anti-CD4 sdAb or scFv composition described herein is used to deliver a CAR or TCR. In some embodiments, the viral vector transduces a cell expressing CD4 (e.g., a CD4+ T cell) and expresses and amplifies the CAR or TCR. The amplified CAR or TCR T cells then mediate targeted cell killing. Thus, the disclosure includes the use of viral vector comprising an anti-CD4 scFv fusogen construct to elicit an immune response specific to the antigen binding moiety of the CAR or TCR. In some embodiments, the CAR is used to target a tumor antigen selected from CD19, CD20, CD22, or BCMA. In another embodiment, the CAR is engineered to comprise an intracellular signaling domain of the T cell antigen receptor complex zeta chain (e.g., CD3 zeta). In a preferred embodiment, the intracellular domain is selected from a CD137 (4-1BB) signaling domain, a CD28 signaling domain, and a CD3zeta signaling domain.

Engineered Receptor Payloads

In some embodiments, the targeted lipid particles (e.g. targeted viral vectors) disclosed herein encode an engineered receptor. In some embodiments, the cells for use in or administered in connection with the provided methods contain or are engineered to contain an engineered receptor, e.g., an engineered antigen receptor, such as a chimeric antigen receptor (CAR). Also provided are populations of such cells, compositions containing such cells and/or enriched for such cells, such as in which cells of a certain type such as T cells or CD4+ cells are enriched or selected. Among the compositions are pharmaceutical compositions and formulations for administration, such as for adoptive cell therapy. Also provided are therapeutic methods for administering the cells and compositions to subjects, e.g., patients, in accord with the provided methods, and/or with the provided articles of manufacture or compositions.

In some embodiments, gene transfer is accomplished without first stimulating the cells, such as by combining it with a stimulus that induces a response such as proliferation, survival, and/or activation, e.g., as measured by expression of a cytokine or activation marker, followed by introduction of the nucleic acids, e.g., by transduction, into the stimulated cells, and optionally incubation or expansion in culture to numbers sufficient for clinical applications.

The viral vectors may express recombinant receptors, such as antigen receptors including chimeric antigen receptors (CARs), and other antigen-binding receptors such as transgenic T cell receptors (TCRs). Also among the receptors are other chimeric receptors.

a. Chimeric Antigen Receptors (CARs)

In some embodiments of the provided methods and uses, chimeric receptors, such as a CARs, contain one or more domains that combine an antigen- or ligand-binding domain (e.g. antibody or antibody fragment) that provides specificity for a desired antigen (e.g., tumor antigen) with intracellular signaling domains. In some embodiments, the intracellular signaling domain is a stimulating or an activating intracellular domain portion, such as a T cell stimulating or activating domain, providing a primary activation signal or a primary signal. In some embodiments, the intracellular signaling domain contains or additionally contains a costimulatory signaling domain to facilitate effector functions. In some embodiments, chimeric receptors when genetically engineered into immune cells modulate T cell activity, and, in some cases, modulate T cell differentiation or homeostasis, thereby resulting in genetically engineered cells with improved longevity, survival and/or persistence in vivo, such as for use in adoptive cell therapy methods.

Exemplary antigen receptors, including CARs, and methods for engineering and introducing such receptors into cells, include those described, for example, in W0200014257, WO2013126726, WO2012/129514, WO2014031687, WO2013/166321, WO2013/071154, WO2013/123061, U.S. patent app. Pub. Nos. US2002131960, US2013287748, US20130149337, U.S. Pat. Nos. 6,451,995, 7,446,190, 8,252,592, 8,339,645, 8,398,282, 7,446,179, 6,410,319, 7,070,995, 7,265,209, 7,354,762, 7,446,191, 8,324,353, and 8,479,118, and European patent app. No. EP2537416, and/or those described by Sadelain et al., Cancer Discov. 2013 April; 3(4): 388-398; Davila et al. (2013) PLOS ONE 8(4):e61338; Turtle et al., Curr. Opin. Immunol., 2012 October; 24(5): 633-39; Wu et al., Cancer, 2012 Mar. 18(2): 160-75. In some aspects, the antigen receptors include a CAR as described in U.S. Pat. No. 7,446,190, and those described in WO/2014055668. Examples of the CARs include CARs as disclosed in any of the aforementioned publications, such as WO2014031687, U.S. Pat. Nos. 8,339,645, 7,446,179, US 2013/0149337, U.S. Pat. Nos. 7,446,190, 8,389,282, Kochenderfer et al., (2013) Nature Reviews Clinical Oncology, 10, 267-276; Wang et al. (2012) J. Immunother. 35(9): 689-701; and Brentjens et al., Sci Transl Med. 2013 5(177). See also WO2014031687, U.S. Pat. Nos. 8,339,645, 7,446,179, US 2013/0149337, U.S. Pat. Nos. 7,446,190, and 8,389,282. The recombinant receptors, such as CARs, generally include an extracellular antigen binding domain, such as a portion of an antibody molecule, generally a variable heavy (VH) chain region and/or variable light (VL) chain region of the antibody, e.g., an scFv antibody fragment. In some embodiments, the antigen binding domain of the CAR molecule comprises an antibody, an antibody fragment, an scFv, a Fv, a Fab, a (Fab′)2, a single domain antibody (SdAb), a VH or VL domain, or a camelid VHH domain.

In some embodiments, the antigen targeted by the receptor is a polypeptide. In some embodiments, it is a carbohydrate or other molecule. In some embodiments, the antigen is selectively expressed or overexpressed on cells of the disease or condition, e.g., the tumor or pathogenic cells, as compared to normal or non-targeted cells or tissues. In other embodiments, the antigen is expressed on normal cells and/or is expressed on the engineered cells.

In some embodiments, the antigen targeted by the receptor includes antigens associated with a B cell malignancy, such as any of a number of known B cell marker. In some embodiments, the antigen targeted by the receptor is CD20, CD19, CD22, ROR1, CD45, CD47, CD21, CD5, CD33, Igkappa, Iglambda, CD79a, CD79b or CD30.

In some embodiments, the chimeric antigen receptor includes an extracellular portion containing an antibody or antibody fragment. In some aspects, the chimeric antigen receptor includes an extracellular portion containing the antibody or fragment and an intracellular signaling domain. In some embodiments, the antibody or fragment includes an scFv.

In some embodiments, the antigen targeted by the antigen-binding domain is CD19. In some aspects, the antigen-binding domain of the recombinant receptor, e.g., CAR, and the antigen-binding domain binds, such as specifically binds or specifically recognizes, a CD19, such as a human CD19. In some embodiments, the scFv contains a VH and a VL derived from an antibody or an antibody fragment specific to CD19. In some embodiments, the antibody or antibody fragment that binds CD19 is a mouse derived antibody such as FMC63 and SJ25C1. In some embodiments, the antibody or antibody fragment is a human antibody, e.g., as described in U.S. Patent Publication No. US 2016/0152723.

In some embodiments, the antigen is CD19. In some embodiments, the scFv contains a VH and a VL derived from an antibody or an antibody fragment specific to CD19. In some embodiments, the antibody or antibody fragment that binds CD19 is a mouse derived antibody such as FMC63 and SJ25C1. In some embodiments, the antibody or antibody fragment is a human antibody, e.g., as described in U.S. Patent Publication No. US 2016/0152723.

In some embodiments, the scFv is derived from FMC63. FMC63 generally refers to a mouse monoclonal IgGI antibody raised against Nalm-1 and -16 cells expressing CD19 of human origin (Fing, N. R., et al. (1987). Leucocyte typing III. 302).

In some embodiments, the antigen targeted by the antigen-binding domain is BCMA. In some aspects, the antigen-binding domain of the recombinant receptor, e.g., CAR, and the antigen-binding domain binds, such as specifically binds or specifically recognizes, a BCMA, such as a human BCMA. In some embodiments, the antigen-binding domain is a fully human VH sdAb disclosed in US2020/0138865 (disclosed herein by reference in its entirety), e.g., FHVH74, FHVH32, FHVH33, or FHVH93.

Antigen Binding Domain (ABD) Targets an Antigen Characteristic of a Neoplastic or Cancer Cell

In some embodiments, the antigen binding domain (ABD) targets an antigen characteristic of a neoplastic cell. In other words, the antigen binding domain targets an antigen expressed by a neoplastic or cancer cell. In some embodiments, the ABD binds a tumor associated antigen. In some embodiments, the antigen characteristic of a neoplastic cell (e.g., antigen associated with a neoplastic or cancer cell) or a tumor associated antigen is selected from a cell surface receptor, an ion channel-linked receptor, an enzyme-linked receptor, a G protein-coupled receptor, receptor tyrosine kinase, tyrosine kinase associated receptor, receptor-like tyrosine phosphatase, receptor serine/threonine kinase, receptor guanylyl cyclase, histidine kinase associated receptor, epidermal growth factor receptors (EGFR) (including ErbB1/EGFR, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4), fibroblast growth factor receptors (FGFR) (including FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF18, and FGF21), vascular endothelial growth factor receptors (VEGFR) (including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PIGF), RET Receptor and the Eph Receptor Family (including EphA1, EphA2, EphA3, EphA4, EphA5, EphA6, EphA7, EphA8, EphA9, EphA10, EphB1, EphB2. EphB3, EphB4, and EphB6), CXCR1, CXCR2, CXCR3, CXCR4, CXCR6, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CFTR, CIC-1, CIC-2, CIC-4, CIC-5, CIC-7, CIC-Ka, CIC-Kb, Bestrophins, TMEM16A, GABA receptor, glycin receptor, ABC transporters, NAV1.1, NAV1.2, NAV1.3, NAV1.4, NAV1.5, NAV1.6, NAV1.7, NAV1.8, NAV1.9, sphingosin-1-phosphate receptor (S1P1R), NMDA channel, transmembrane protein, multispan transmembrane protein, T-cell receptor motifs, T-cell alpha chains, T-cell β chains, T-cell γ chains, T-cell δ chains, CCR7, CD3, CD4, CD5, CD7, CD8, CD11b, CD11c, CD16, CD19, CD20, CD21, CD22, CD25, CD28, CD34, CD35, CD40, CD45RA, CD45RO, CD52, CD56, CD62L, CD68, CD80, CD95, CD117, CD127, CD133, CD137 (4-1BB), CD163, F4/80, IL-4Ra, Sca-1, CTLA-4, GITR, GARP, LAP, granzyme B, LFA-1, transferrin receptor, NKp46, perforin, CD4+, Th1, Th2, Th17, Th40, Th22, Th9, Tfh, canonical Treg. FoxP3+, Tr1, Th3, Treg17, TREG; CDCP, NT5E, EpCAM, CEA, gpA33, mucins, TAG-72, carbonic anhydrase IX, PSMA, folate binding protein, gangliosides (e.g., CD2, CD3, GM2), Lewis-γ², VEGF, VEGFR 1/2/3, αVβ3, α5β1, ErbB1/EGFR, ErbB1/HER2, ErB3, c-MET, IGF1R, EphA3, TRAIL-R1, TRAIL-R2, RANKL, FAP, Tenascin, PDL-1, BAFF, HDAC, ABL, FLT3, KIT, MET, RET, IL-1β, ALK, RANKL, mTOR, CTLA-4, IL-6, IL-6R, JAK3, BRAF, PTCH, Smoothened, PIGF, ANPEP, TIMP1, PLAUR, PTPRJ, LTBR, ANTXR1, folate receptor alpha (FRa), ERBB2 (Her2/neu), EphA2, IL-13Ra2, epidermal growth factor receptor (EGFR), mesothelin, TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII, GD2, GD3, BCMA, MUC16 (CA125), L1CAM, LeY, MSLN, IL13Rα1, L1-CAM, Tn Ag, prostate specific membrane antigen (PSMA), ROR1, FLT3, FAP, TAG72, CD38, CD44v6, CEA, EPCAM, B7H3, KIT, interleukin-11 receptor a (IL-11Ra), PSCA, PRSS21, VEGFR2, LewisY, CD24, platelet-derived growth factor receptor-beta (PDGFR-beta), SSEA-4, CD20, MUC1, NCAM, Prostase, PAP, ELF2M, Ephrin B2, IGF-1 receptor, CAIX, LMP2, gpl00, bcr-abl, tyrosinase, Fucosyl GM1, sLe, GM3, TGS5, HMWMAA, o-acetyl-GD2, folate receptor beta, TEM1/CD248, TEM7R, CLDN6, GPRC5D, CXORF61, CD97, CD179a, ALK, Polysialic acid, PLACI, GloboH, NY-BR-1, UPK2, HAVCR1, ADRB3, PANX3, GPR20, LY6K, OR51E2, TARP, WT1, NY-ESO-1, LAGE-la, MAGE-A1, legumain, HPV E6, E7, ETV6-AML, sperm protein 17, XAGE1, Tie 2, MAD-CT-1, MAD-CT-2, major histocompatibility complex class I-related gene protein (MR1), urokinase-type plasminogen activator receptor (uPAR), Fos-related antigen 1, p53, p53 mutant, prostein, survivin, telomerase, PCTA-1/Galectin 8, MelanA/MART1, Ras mutant, hTERT, sarcoma translocation breakpoints, ML-IAP, ERG (TMPRSS2 ETS fusion gene), NA17, PAX3, androgen receptor, cyclin B1, MYCN, RhoC, TRP-2, CYPIB I, BORIS, SART3, PAX5, OY-TES1, LCK, AKAP-4, SSX2, RAGE-1, human telomerase reverse transcriptase, RU1, RU2, intestinal carboxyl esterase, mut hsp70-2, CD79a, CD79b, CD72, LAIR1, FCAR, LILRA2, CD300LF, CLEC12A, BST2, EMR2, LY75, GPC3, FCRL5, IGLL1, a neoantigen, CD133, CD15, CD184, CD24, CD56, CD26, CD29, CD44, HLA-A, HLA-B, HLA-C, (HLA-A,B,C) CD49f, CD151 CD340, CD200, tkrA, trkB, or trkC, or an antigenic fragment or antigenic portion thereof.

ABD Targets an Antigen Characteristic of a T Cell

In some embodiments, the antigen binding domain targets an antigen characteristic of a T cell. In some embodiments, the ABD binds an antigen associated with a T cell. In some instances, such an antigen is expressed by a T cell or is located on the surface of a T cell. In some embodiments, the antigen characteristic of a T cell or the T cell associated antigen is selected from a cell surface receptor, a membrane transport protein (e.g., an active or passive transport protein such as, for example, an ion channel protein, a pore-forming protein, etc.), a transmembrane receptor, a membrane enzyme, and/or a cell adhesion protein characteristic of a T cell. In some embodiments, an antigen characteristic of a T cell is a G protein-coupled receptor, receptor tyrosine kinase, tyrosine kinase associated receptor, receptor-like tyrosine phosphatase, receptor serine/threonine kinase, receptor guanylyl cyclase, histidine kinase associated receptor, AKT1; AKT2; AKT3; ATF2; BCL10; CALM1; CD3D (CD30); CD3E (CD38); CD3G (CD3γ); CD4; CD8; CD28; CD45; CD80 (B7-1); CD86 (B7-2); CD247 (CD32); CTLA-4 (CD152); ELK1; ERK1 (MAPK3); ERK2; FOS; FYN; GRAP2 (GADS); GRB2; HLA-DRA; HLA-DRB1; HLA-DRB3; HLA-DRB4; HLA-DRB5; HRAS; IKBKA (CHUK); IKBKB; IKBKE; IKBKG (NEMO); IL2; ITPR1; ITK; JUN; KRAS2; LAT; LCK; MAP2K1 (MEK1); MAP2K2 (MEK2); MAP2K3 (MKK3); MAP2K4 (MKK4); MAP2K6 (MKK6); MAP2K7 (MKK7); MAP3K1 (MEKK1); MAP3K3; MAP3K4; MAP3K5; MAP3K8; MAP3K14 (NIK); MAPK8 (JNK1); MAPK9 (JNK2); MAPK10 (JNK3); MAPK11 (p383); MAPK12 (p38γ); MAPK13 (p380); MAPK14 (p38a); NCK; NFAT1; NFAT2; NFKB1; NFKB2; NFKBIA; NRAS; PAK1; PAK2; PAK3; PAK4; PIK3C2B; PIK3C3 (VPS34); PIK3CA; PIK3CB; PIK3CD; PIK3R1; PKCA; PKCB; PKCM; PKCQ; PLCY1; PRF1 (Perforin); PTEN; RAC1; RAF1; RELA; SDF1; SHP2; SLP76; SOS; SRC; TBK1; TCRA; TEC; TRAF6; VAV1; VAV2; or ZAP70.

ABD Targets an Antigen Characteristic of an Autoimmune or Inflammatory Disorder

In some embodiments, the antigen binding domain targets an antigen characteristic of an autoimmune or inflammatory disorder. In some embodiments, the ABD binds an antigen associated with an autoimmune or inflammatory disorder. In some instances, the antigen is expressed by a cell associated with an autoimmune or inflammatory disorder. In some embodiments, the autoimmune or inflammatory disorder is selected from chronic graft-vs-host disease (GVHD), lupus, arthritis, immune complex glomerulonephritis, goodpasture syndrome, uveitis, hepatitis, systemic sclerosis or scleroderma, type I diabetes, multiple sclerosis, cold agglutinin disease, Pemphigus vulgaris, Grave's disease, autoimmune hemolytic anemia, Hemophilia A, Primary Sjogren's Syndrome, thrombotic thrombocytopenia purrpura, neuromyelits optica, Evan's syndrome, IgM mediated neuropathy, cryoglobulinemia, dermatomyositis, idiopathic thrombocytopenia, ankylosing spondylitis, bullous pemphigoid, acquired angioedema, chronic urticarial, antiphospholipid demyelinating polyneuropathy, and autoimmune thrombocytopenia or neutropenia or pure red cell aplasias, while exemplary non-limiting examples of alloimmune diseases include allosensitization (see, for example, Blazar et al., 2015, Am. J. Transplant, 15(4):931-41) or xenosensitization from hematopoietic or solid organ transplantation, blood transfusions, pregnancy with fetal allosensitization, neonatal alloimmune thrombocytopenia, hemolytic disease of the newborn, sensitization to foreign antigens such as can occur with replacement of inherited or acquired deficiency disorders treated with enzyme or protein replacement therapy, blood products, and gene therapy. In some embodiments, the antigen characteristic of an autoimmune or inflammatory disorder is selected from a cell surface receptor, an ion channel-linked receptor, an enzyme-linked receptor, a G protein-coupled receptor, receptor tyrosine kinase, tyrosine kinase associated receptor, receptor-like tyrosine phosphatase, receptor serine/threonine kinase, receptor guanylyl cyclase, or histidine kinase associated receptor.

In some embodiments, an antigen binding domain of a CAR binds to a ligand expressed on B cells, plasma cells, or plasmablasts. In some embodiments, an antigen binding domain of a CAR binds to CD10, CD19, CD20, CD22, CD24, CD27, CD38, CD45R, CD138, CD319, BCMA, CD28, TNF, interferon receptors, GM-CSF, ZAP-70, LFA-1, CD3 gamma, CD5 or CD2. See, e.g., US 2003/0077249; WO 2017/058753; WO 2017/058850, the contents of which are herein incorporated by reference.

ABD Targets an Antigen Characteristic of Senescent Cells

In some embodiments, the antigen binding domain targets an antigen characteristic of senescent cells, e.g., urokinase-type plasminogen activator receptor (uPAR). In some embodiments, the ABD binds an antigen associated with a senescent cell. In some instances, the antigen is expressed by a senescent cell. In some embodiments, the CAR is used for treatment or prophylaxis of disorders characterized by the aberrant accumulation of senescent cells, e.g., liver and lung fibrosis, atherosclerosis, diabetes and osteoarthritis.

ABD Targets an Antigen Characteristic of an Infectious Disease

In some embodiments, the antigen binding domain targets an antigen characteristic of an infectious disease. In some embodiments, the ABD binds an antigen associated with an infectious disease. In some instances, the antigen is expressed by a cell affected by an infectious disease. In some embodiments, wherein the infectious disease is selected from HIV, hepatitis B virus, hepatitis C virus, Human herpes virus, Human herpes virus 8 (HHV-8, Kaposi sarcoma-associated herpes virus (KSHV)), Human T-lymphotrophic virus-1 (HTLV-1), Merkel cell polyomavirus (MCV), Simian virus 40 (SV40), Epstein-Barr virus, CMV, human papillomavirus. In some embodiments, the antigen characteristic of an infectious disease is selected from a cell surface receptor, an ion channel-linked receptor, an enzyme-linked receptor, a G protein-coupled receptor, receptor tyrosine kinase, tyrosine kinase associated receptor, receptor-like tyrosine phosphatase, receptor serine/threonine kinase, receptor guanylyl cyclase, histidine kinase associated receptor, HIV Env, gpl20, or CD4-induced epitope on HIV-1 Env.

ABD Binds to a Cell Surface Antigen of a Cell

In some embodiments, an antigen binding domain binds to a cell surface antigen of a cell. In some embodiments, a cell surface antigen is characteristic of (e.g., expressed by) a particular or specific cell type. In some embodiments, a cell surface antigen is characteristic of more than one type of cell.

In some embodiments, a CAR antigen binding domain binds a cell surface antigen characteristic of a T cell, such as a cell surface antigen on a T cell. In some embodiments, an antigen characteristic of a T cell is a cell surface receptor, a membrane transport protein (e.g., an active or passive transport protein such as, for example, an ion channel protein, a pore-forming protein, etc.), a transmembrane receptor, a membrane enzyme, and/or a cell adhesion protein characteristic of a T cell. In some embodiments, an antigen characteristic of a T cell is a G protein-coupled receptor, receptor tyrosine kinase, tyrosine kinase associated receptor, receptor-like tyrosine phosphatase, receptor serine/threonine kinase, receptor guanylyl cyclase, or histidine kinase associated receptor.

In some embodiments, an antigen binding domain of a CAR binds a T cell receptor. In some embodiments, a T cell receptor is AKT1; AKT2; AKT3; ATF2; BCL10; CALM1; CD3D (CD30); CD3E (CD38); CD3G (CD3γ); CD4; CD8; CD28; CD45; CD80 (B7-1); CD86 (B7-2); CD247 (CD3ζ); CTLA-4 (CD152); ELK1; ERK1 (MAPK3); ERK2; FOS; FYN; GRAP2 (GADS); GRB2; HLA-DRA; HLA-DRB1; HLA-DRB3; HLA-DRB4; HLA-DRB5; HRAS; IKBKA (CHUK); IKBKB; IKBKE; IKBKG (NEMO); IL2; ITPR1; ITK; JUN; KRAS2; LAT; LCK; MAP2K1 (MEK1); MAP2K2 (MEK2); MAP2K3 (MKK3); MAP2K4 (MKK4); MAP2K6 (MKK6); MAP2K7 (MKK7); MAP3K1 (MEKK1); MAP3K3; MAP3K4; MAP3K5; MAP3K8; MAP3K14 (NIK); MAPK8 (JNK1); MAPK9 (JNK2); MAPK10 (JNK3); MAPK11 (p38B); MAPK12 (p38γ); MAPK13 (p380); MAPK14 (p38a); NCK; NFAT1; NFAT2; NFKB1; NFKB2; NFKBIA; NRAS; PAK1; PAK2; PAK3; PAK4; PIK3C2B; PIK3C3 (VPS34); PIK3CA; PIK3CB; PIK3CD; PIK3R1; PKCA; PKCB; PKCM; PKCQ; PLCY1; PRF1 (Perforin); PTEN; RAC1; RAF1; RELA; SDF1; SHP2; SLP76; SOS; SRC; TBK1; TCRA; TEC; TRAF6; VAV1; VAV2; or ZAP70.

Transmembrane Domain

In some embodiments, the CAR transmembrane domain comprises at least a transmembrane region of the alpha, beta or zeta chain of a T cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, or functional variant thereof. In some embodiments, the transmembrane domain comprises at least a transmembrane region(s) of CD4, 4-1BB/CD137, CD28, CD34, CD4, FcεRIγ, CD16, OX40/CD134, CD3ζ, CD3ε, CD3γ, CD3δ, TCRα, TCRβ, TCRζ, CD32, CD64, CD64, CD45, CD5, CD9, CD22, CD37, CD80, CD86, CD40, CD40L/CD154, VEGFR2, FAS, and FGFR2B, or functional variant thereof. antigen binding domain binds

Signaling Domain or Plurality of Signaling Domains

In some embodiments, a CAR described herein comprises one or at least one signaling domain selected from one or more of B7-1/CD80; B7-2/CD86; B7-H1/PD-L1; B7-H2; B7-H3; B7-H4; B7-H6; B7-H7; BTLA/CD272; CD28; CTLA-4; Gi24/VISTA/B7-H5; ICOS/CD278; PD-1; PD-L2/B7-DC; PDCD6); 4-1BB/TNFSF9/CD137; 4-1BB Ligand/TNFSF9; BAFF/BLyS/TNFSF13B; BAFF R/TNFRSF13C; CD27/TNFRSF7; CD27 Ligand/TNFSF7; CD30/TNFRSF8; CD30 Ligand/TNFSF8; CD40/TNFRSF5; CD40/TNFSF5; CD40 Ligand/TNFSF5; DR3/TNFRSF25; GITR/TNFRSF18; GITR Ligand/TNFSF18; HVEM/TNFRSF14; LIGHT/TNFSF14; Lymphotoxin-alpha/TNF-beta; OX40/TNFRSF4; OX40 Ligand/TNFSF4; RELT/TNFRSF19L; TACI/TNFRSF13B; TL1A/TNFSF15; TNF-alpha; TNF RII/TNFRSF1B); 2B4/CD244/SLAMF4; BLAME/SLAMF8; CD2; CD2F-10/SLAMF9; CD48/SLAMF2; CD58/LFA-3; CD84/SLAMF5; CD229/SLAMF3; CRACC/SLAMF7; NTB-A/SLAMF6; SLAM/CD150); CD2; CD7; CD53; CD82/Kai-1; CD90/Thyl; CD96; CD160; CD200; CD300a/LMIR1; HLA Class I; HLA-DR; Ikaros; Integrin alpha 4/CD49d; Integrin alpha 4 beta 1; Integrin alpha 4 beta 7/LPAM-1; LAG-3; TCL1A; TCL1B; CRTAM; DAP12; Dectin-1/CLEC7A; DPPIV/CD26; EphB6; TIM-1/KIM-1/HAVCR; TIM-4; TSLP; TSLP R; lymphocyte function associated antigen-1 (LFA-1); NKG2C, a CD3 zeta domain, an immunoreceptor tyrosine-based activation motif (ITAM), CD27, CD28, 4-1BB, CD134/OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, or functional fragment thereof.

In some embodiments, the at least one signaling domain comprises a CD3 zeta domain or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof. In other embodiments, the at least one signaling domain comprises (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; and (ii) a CD28 domain, or a 4-1BB domain, or functional variant thereof. In yet other embodiments, the at least one signaling domain comprises a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; and (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof. In some embodiments, the at least one signaling domain comprises a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof; and (iv) a cytokine or costimulatory ligand transgene.

In some embodiments, the at least two signaling domains comprise a CD3 zeta domain or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof. In other embodiments, the at least two signaling domains comprise (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; and (ii) a CD28 domain, or a 4-1BB domain, or functional variant thereof. In yet other embodiments, the at least one signaling domain comprises a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; and (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof. In some embodiments, the at least two signaling domains comprise a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof; and (iv) a cytokine or costimulatory ligand transgene.

In some embodiments, the at least three signaling domains comprise a CD3 zeta domain or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof. In other embodiments, the at least three signaling domains comprise (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; and (ii) a CD28 domain, or a 4-1BB domain, or functional variant thereof. In yet other embodiments, the least three signaling domains comprises a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; and (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof. In some embodiments, the at least three signaling domains comprise a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof; and (iv) a cytokine or costimulatory ligand transgene.

In some embodiments, the CAR comprises a CD3 zeta domain or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof. In some embodiments, the CAR comprises (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; and (ii) a CD28 domain, or a 4-1BB domain, or functional variant thereof.

In some embodiments, the CAR comprises a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; and (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof.

In some embodiments, the CAR comprises (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain, or a 4-1BB domain, or functional variant thereof, and/or (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof.

In some embodiments, the CAR comprises a (i) a CD3 zeta domain, or an immunoreceptor tyrosine-based activation motif (ITAM), or functional variant thereof; (ii) a CD28 domain or functional variant thereof; (iii) a 4-1BB domain, or a CD134 domain, or functional variant thereof; and (iv) a cytokine or costimulatory ligand transgene.

Domain which Upon Successful Signaling of the CAR Induces Expression of a Cytokine Gene

In some embodiments, a first, second, third, or fourth generation CAR further comprises a domain which upon successful signaling of the CAR induces expression of a cytokine gene. In some embodiments, a cytokine gene is endogenous or exogenous to a target cell comprising a CAR which comprises a domain which upon successful signaling of the CAR induces expression of a cytokine gene. In some embodiments, a cytokine gene encodes a pro-inflammatory cytokine. In some embodiments, a cytokine gene encodes IL-1, IL-2, IL-9, IL-12, IL-18, TNF, or IFN-gamma, or functional fragment thereof. In some embodiments, a domain which upon successful signaling of the CAR induces expression of a cytokine gene is or comprises a transcription factor or functional domain or fragment thereof. In some embodiments, a domain which upon successful signaling of the CAR induces expression of a cytokine gene is or comprises a transcription factor or functional domain or fragment thereof. In some embodiments, a transcription factor or functional domain or fragment thereof is or comprises a nuclear factor of activated T cells (NFAT), an NF-kB, or functional domain or fragment thereof. See, e.g., Zhang. C. et al., Engineering CAR-T cells. Biomarker Research. 5:22 (2017); WO 2016126608; Sha, H. et al. Chimaeric antigen receptor T-cell therapy for tumour immunotherapy. Bioscience Reports Jan. 27, 2017, 37 (1).

In some embodiments, the CAR further comprises one or more spacers, e.g., wherein the spacer is a first spacer between the antigen binding domain and the transmembrane domain. In some embodiments, the first spacer includes at least a portion of an immunoglobulin constant region or variant or modified version thereof. In some embodiments, the spacer is a second spacer between the transmembrane domain and a signaling domain. In some embodiments, the second spacer is an oligopeptide, e.g., wherein the oligopeptide comprises glycine and serine residues such as but not limited to glycine-serine doublets. In some embodiments, the CAR comprises two or more spacers, e.g., a spacer between the antigen binding domain and the transmembrane domain and a spacer between the transmembrane domain and a signaling domain.

In some embodiments, any one of the cells described herein comprises a nucleic acid encoding a CAR or a first generation CAR. In some embodiments, a first generation CAR comprises an antigen binding domain, a transmembrane domain, and signaling domain. In some embodiments, a signaling domain mediates downstream signaling during T cell activation.

In some embodiments, the methods and compositions disclosed herein comprise a nucleic acid encoding a CAR or a second generation CAR. In some embodiments, a second generation CAR comprises an antigen binding domain, a transmembrane domain, and two signaling domains. In some embodiments, a signaling domain mediates downstream signaling during T cell activation. In some embodiments, a signaling domain is a costimulatory domain. In some embodiments, a costimulatory domain enhances cytokine production, CAR-T cell proliferation, and/or CAR-T cell persistence during T cell activation.

In some embodiments, any one of the compositions and methods described herein comprises a nucleic acid encoding a CAR or a third generation CAR. In some embodiments, a third generation CAR comprises an antigen binding domain, a transmembrane domain, and at least three signaling domains. In some embodiments, a signaling domain mediates downstream signaling during T cell activation. In some embodiments, a signaling domain is a costimulatory domain. In some embodiments, a costimulatory domain enhances cytokine production, CAR-T cell proliferation, and or CAR-T cell persistence during T cell activation. In some embodiments, a third generation CAR comprises at least two costimulatory domains. In some embodiments, the at least two costimulatory domains are not the same.

In some embodiments, any one of the compositions and methods described herein comprises a nucleic acid encoding a CAR or a fourth generation CAR. In some embodiments, a fourth generation CAR comprises an antigen binding domain, a transmembrane domain, and at least two, three, or four signaling domains. In some embodiments, a signaling domain mediates downstream signaling during T cell activation. In some embodiments, a signaling domain is a costimulatory domain. In some embodiments, a costimulatory domain enhances cytokine production, CAR-T cell proliferation, and or CAR-T cell persistence during T cell activation.

Abd Comprising an Antibody or Antigen-Binding Portion Thereof

In some embodiments, a CAR antigen binding domain is or comprises an antibody or antigen-binding portion thereof. In some embodiments, a CAR antigen binding domain is or comprises an scFv or Fab. In some embodiments, a CAR antigen binding domain comprises an scFv or Fab fragment of a CD19 antibody; CD22 antibody; T-cell alpha chain antibody; T-cell β chain antibody; T-cell γ chain antibody; T-cell δ chain antibody; CCR7 antibody; CD3 antibody; CD4 antibody; CD5 antibody; CD7 antibody; CD8 antibody; CD11b antibody; CD11c antibody; CD16 antibody; CD20 antibody; CD21 antibody; CD25 antibody; CD28 antibody; CD34 antibody; CD35 antibody; CD40 antibody; CD45RA antibody; CD45RO antibody; CD52 antibody; CD56 antibody; CD62L antibody; CD68 antibody; CD80 antibody; CD95 antibody; CD117 antibody; CD127 antibody; CD133 antibody; CD137 (4-1 BB) antibody; CD163 antibody; F4/80 antibody; IL-4Ra antibody; Sca-1 antibody; CTLA-4 antibody; GITR antibody GARP antibody; LAP antibody; granzyme B antibody; LFA-1 antibody; MR1 antibody; uPAR antibody; or transferrin receptor antibody.

In some embodiments, a CAR comprises a signaling domain which is a costimulatory domain. In some embodiments, a CAR comprises a second costimulatory domain. In some embodiments, a CAR comprises at least two costimulatory domains. In some embodiments, a CAR comprises at least three costimulatory domains. In some embodiments, a CAR comprises a costimulatory domain selected from one or more of CD27, CD28, 4-1BB, CD134/OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83. In some embodiments, if a CAR comprises two or more costimulatory domains, two costimulatory domains are different. In some embodiments, if a CAR comprises two or more costimulatory domains, two costimulatory domains are the same.

In addition to the CARs described herein, various chimeric antigen receptors and nucleotide sequences encoding the same are known in the art and would be suitable for fusosomal delivery and reprogramming of target cells in vivo and in vitro as described herein. See, e.g., WO2013040557; WO2012079000; WO2016030414; Smith T, et al., Nature Nanotechnology. 2017. DOI: 10.1038/NNANO.2017.57, the disclosures of which are herein incorporated by reference.

Additional Descriptions of CARS

In certain embodiments, the compositions and methods comprise a polynucleotide encoding a CAR. CARs (also known as chimeric immunoreceptors, chimeric T cell receptors, or artificial T cell receptors) are receptor proteins that have been engineered to give host cells (e.g., T cells) the new ability to target a specific protein. The receptors are chimeric because they combine both antigen-binding and T cell activating functions into a single receptor. The polycistronic vector of the present disclosure may be used to express one or more CARs in a host cell (e.g., a T cell) for use in therapies against various target antigens. The CARs expressed by the one or more expression cassettes may be the same or different. In these embodiments, the CAR comprises an extracellular binding domain (also referred to as a “binder”) that specifically binds a target antigen, a transmembrane domain, and an intracellular signaling domain. In certain embodiments, the CAR further comprises one or more additional elements, including one or more signal peptides, one or more extracellular hinge domains, and/or one or more intracellular costimulatory domains. Domains may be directly adjacent to one another, or there may be one or more amino acids linking the domains. The nucleotide sequence encoding a CAR may be derived from a mammalian sequence, for example, a mouse sequence, a primate sequence, a human sequence, or combinations thereof. In the cases where the nucleotide sequence encoding a CAR is non-human, the sequence of the CAR may be humanized. The nucleotide sequence encoding a CAR may also be codon-optimized for expression in a mammalian cell, for example, a human cell. In any of these embodiments, the nucleotide sequence encoding a CAR may be at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to any of the nucleotide sequences disclosed herein. The sequence variations may be due to codon-optimalization, humanization, restriction enzyme-based cloning scars, and/or additional amino acid residues linking the functional domains, etc.

In certain embodiments, the CAR comprises a signal peptide at the N-terminus. Non-limiting examples of signal peptides include CD4 signal peptide, IgK signal peptide, and granulocyte-macrophage colony-stimulating factor receptor subunit alpha (GMCSFR-α, also known as colony stimulating factor 2 receptor subunit alpha (CSF2RA)) signal peptide, and variants thereof, the amino acid sequences of which are provided in Table 3 below.

TABLE 3
Exemplary sequences of signal peptides

	SEQ ID
	NO:	Sequence	Description
	14003	MALPVTALLLPLALLLHA	CD8α signal
		ARP	peptide
	14004	METDTLLLWVLLLWVPGS	IgK signal
		TG	peptide
	14005	MLLLVTSLLLCELPHPAF	GMCSFR-α (CSF2RA)
		LLIP	signal peptide

In certain embodiments, the extracellular binding domain of the CAR comprises one or more antibodies specific to one target antigen or multiple target antigens. The antibody may be an antibody fragment, for example, an scFv, or a single-domain antibody fragment, for example, a VHH. In certain embodiments, the scFv may comprise a heavy chain variable region (V_H) and a light chain variable region (V_L) of an antibody connected by a linker. The V_H and the V_L may be connected in either order, i.e., V_H-linker-V_L or V_L-linker-V_H. Non-limiting examples of linkers include Whitlow linker, (G4S) n (n can be a positive integer, e.g., 1, 2, 3, 4, 5, 6, etc. (SEQ ID NO: 14127)) linker, and variants thereof. In certain embodiments, the antigen is an antigen that is exclusively or preferentially expressed on tumor cells, or an antigen that is characteristic of an autoimmune or inflammatory disease. Exemplary target antigens include, but are not limited to, CD5, CD19, CD20, CD22, CD23, CD30, CD70, Kappa, Lambda, and B cell maturation agent (BCMA), G-protein coupled receptor family C group 5 member D (GPRC5D) (associated with leukemias); CS1/SLAMF7, CD38, CD138, GPRC5D, TACI, and BCMA (associated with myelomas); GD2, HER2, EGFR, EGFRvIII, B7H3, PSMA, PSCA, CAIX, CD171, CEA, CSPG4, EPHA2, FAP, FRa, IL-13Ra, Mesothelin, MUC1, MUC16, and ROR1 (associated with solid tumors). In any of these embodiments, the extracellular binding domain of the CAR is codon-optimized for expression in a host cell or have variant sequences to increase functions of the extracellular binding domain.

In certain embodiments, the CAR comprises a hinge domain, also referred to as a spacer. The terms “hinge” and “spacer” may be used interchangeably in the present disclosure. Non-limiting examples of hinge domains include CD4 hinge domain, CD28 hinge domain, IgG4 hinge domain, IgG4 hinge-CH2-CH3 domain, and variants thereof, the amino acid sequences of which are provided in Table 4 below.

TABLE 4
Exemplary sequences of hinge domains

	SEQ ID
	NO:	Sequence	Description
	14006	TTTPAPRPPTPAPTI-ASQPLSL	CD8α hinge
		RPEACRPAAGGAVHTRGLDFACD	domain
	14007	IEVMYPPPYLDNEKSNGTIIHVK	CD28 hinge
		GKHLCP-SPLFPGPSKP	domain
	14013	AAAIEVMYPPPYLDNEKSNGTII	CD28 hinge
		HVKGKHLCP-SPLFPGPSKP	domain
	14008	ESKYGPPCPPCP	IgG4 hinge
			domain
	14009	ESKYGPPCPSCP	IgG4 hinge
			domain
	14010	ESKYGPPCPPCPAPEFLGGPSVF	IgG4 hinge-
		LFPPKPKD-TLMISRTPEVTCVV	CH2-CH3
		VDVSQEDPEVQFNWY-VDGVEVH	domain
		NAKTKPREEQFNSTYRVVSVLTV
		LHQDWLNGKEYKCKVSNKGLPSS
		IEK-TISKAKGQPREPQVYTLPP
		-SQEEMTKNQVSLTCLVKGFYPS
		DIAVEWESNGQPENNYKTTPPVL
		DSDGSFFLYSRL-TVDKSRWQEG
		NVFSCSVM-HEALHNHYTQKSLS
		LSLGK

In certain embodiments, the transmembrane domain of the CAR comprises a transmembrane region of the alpha, beta, or zeta chain of a T cell receptor, CD28, CD38, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, or a functional variant thereof, including the human versions of each of these sequences. In other embodiments, the transmembrane domain comprises a transmembrane region of CD4, 4-1BB/CD137, CD28, CD34, CD8α, CD8β, FcεRIγ, CD16, OX40/CD134, CD3ζ, CD3ε, CD3γ, CD3δ, TCRα, TCRβ, TCRζ, CD32, CD64, CD64, CD45, CD5, CD9, CD22, CD37, CD80, CD86, CD40, CD40L/CD154, VEGFR2, FAS, and FGFR2B, or a functional variant thereof, including the human versions of each of these sequences. Table 5 provides the amino acid sequences of a few exemplary transmembrane domains.

TABLE 5
Exemplary sequences of transmembrane domains

SEQ ID
NO:	Sequence	Description
14011	IYIWAPLAGTCGVL	CD8α
	LLSLVITLYC	transmembrane
		domain
14012	FWVLVVVGGVLACY	CD28
	SLLVTVAFIIFWV	transmembrane
		domain
14014	MFWVLVVVGGVLAC	CD28
	YSLLVTVAFIIFWV	transmembrane
		domain

In certain embodiments, the intracellular signaling domain and/or intracellular costimulatory domain of the CAR comprises one or more signaling domains selected from B7-1/CD80, B7-2/CD86, B7-H1/PD-L1, B7-H2, B7-H3, B7-H4, B7-H6, B7-H7, BTLA/CD272, CD28, CTLA-4, Gi24/VISTA/B7-H5, ICOS/CD278, PD-1, PD-L2/B7-DC, PDCD6, 4-1BB/TNFSF9/CD137, 4-1BB Ligand/TNFSF9, BAFF/BLyS/TNFSF13B, BAFF R/TNFRSF13C, CD27/TNFRSF7, CD27 Ligand/TNFSF7, CD30/TNFRSF8, CD30 Ligand/TNFSF8, CD40/TNFRSF5, CD40/TNFSF5, CD40 Ligand/TNFSF5, DR3/TNFRSF25, GITR/TNFRSF18, GITR Ligand/TNFSF18, HVEM/TNFRSF14, LIGHT/TNFSF14, Lymphotoxin-alpha/TNFβ, OX40/TNFRSF4, OX40 Ligand/TNFSF4, RELT/TNFRSF19L, TACI/TNFRSF13B, TL1A/TNFSF15, TNFα, TNF RII/TNFRSF1B, 2B4/CD244/SLAMF4, BLAME/SLAMF8, CD2, CD2F-10/SLAMF9, CD48/SLAMF2, CD58/LFA-3, CD84/SLAMF5, CD229/SLAMF3, CRACC/SLAMF7, NTB-A/SLAMF6, SLAM/CD150, CD2, CD7, CD53, CD82/Kai-1, CD90/Thyl, CD96, CD160, CD200, CD300a/LMIR1, HLA Class I, HLA-DR, Ikaros, Integrin alpha 4/CD49d, Integrin alpha 4 beta 1, Integrin alpha 4 beta 7/LPAM-1, LAG-3, TCL1A, TCL1B, CRTAM, DAP12, Dectin-1/CLEC7A, DPPIV/CD26, EphB6, TIM-1/KIM-1/HAVCR, TIM-4, TSLP, TSLP R, lymphocyte function associated antigen-1 (LFA-1), NKG2C, CD3ζ, an immunoreceptor tyrosine-based activation motif (ITAM), CD27, CD28, 4-1BB, CD134/OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and a functional variant thereof including the human versions of each of these sequences. In some embodiments, the intracellular signaling domain and/or intracellular costimulatory domain comprises one or more signaling domains selected from a CD37 domain, an ITAM, a CD28 domain, 4-1BB domain, or a functional variant thereof. Table 6 provides the amino acid sequences of a few exemplary intracellular costimulatory and/or signaling domains. In certain embodiments, as in the case of tisagenlecleucel as described below, the CD34 signaling domain of SEQ ID NO:14017 has a mutation, e.g., a glutamine (Q) to lysine (K) mutation, at amino acid position 14 (see SEQ ID NO:14018).

TABLE 6
Exemplary sequences of intracellular
costimulatory and/or signaling domains

SEQ ID
NO:	Sequence	Description
14015	KRGRKKLLY-IFKQPFMRPVQ	4-1BB costimulatory
	TTQEEDGCSCRF-PEEEEGGC	domain
	EL
14016	RSKRS-RLLHSDYMNMTPRR	CD28 costimulatory
	PGPTRKHYQPYAPPRDFAAY	domain
	RS
14017	RVKFSRSADAPA-YQQGQNQ	CD3ζ signaling
	LYNELNLGR-REEYDVLDKR	domain
	RGRDPEMGGKPRR-KNPQEG
	LYNEL-QKDKMAEAYSEIGM
	KGERRRGKGHDGLYQGLSTA
	TKDTYDALHMQALPPR
14018	RVKFSRSADAPA-YKQGQNQ	CD3ζ signaling
	LYNELNLGR-REEYDVLDKR	domain
	RGRDPEMGGKPRR-KNPQEG	(with Q to K
	LYNEL-QKDKMAEAYSEIGM	mutation at
	KGERRRGKGHDGLYQGLSTA	position 14)
	TKDTYDALHMQALPPR

In certain embodiments where the polycistronic vector encodes two or more CARs, the two or more CARs comprise the same functional domains, or one or more different functional domains, as described. For example, the two or more CARs comprise different signal peptides, extracellular binding domains, hinge domains, transmembrane domains, costimulatory domains, and/or intracellular signaling domains, in order to minimize the risk of recombination due to sequence similarities. Or, alternatively, the two or more CARs comprise the same domains. In the cases where the same domain(s) and/or backbone are used, it is optional to introduce codon divergence at the nucleotide sequence level to minimize the risk of recombination.

CD19 CAR

In some embodiments, the CAR is a CD19 CAR (“CD19-CAR”), and in these embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD19 CAR. In some embodiments, the CD19 CAR comprises a signal peptide, an extracellular binding domain that specifically binds CD19, a hinge domain, a transmembrane domain, an intracellular costimulatory domain, and/or an intracellular signaling domain in tandem.

In some embodiments, the signal peptide of the CD19 CAR comprises a CD4 signal peptide. In some embodiments, the CD4 signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO:14003 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO:14003. In some embodiments, the signal peptide comprises an IgK signal peptide. In some embodiments, the IgK signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14004 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14004. In some embodiments, the signal peptide comprises a GMCSFR-α or CSF2RA signal peptide. In some embodiments, the GMCSFR-α or CSF2RA signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14005 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14005.

In some embodiments, the extracellular binding domain of the CD19 CAR is specific to CD19, for example, human CD19. The extracellular binding domain of the CD19 CAR can be codon-optimized for expression in a host cell or to have variant sequences to increase functions of the extracellular binding domain. In some embodiments, the extracellular binding domain comprises an immunogenically active portion of an immunoglobulin molecule, for example, an scFv.

In some embodiments, the extracellular binding domain of the CD19 CAR comprises an scFv derived from the FMC63 monoclonal antibody (FMC63), which comprises the heavy chain variable region (V_H) and the light chain variable region (V_L) of FMC63 connected by a linker. FMC63 and the derived scFv have been described in Nicholson et al., Mol. Immun. 34(16-17): 1157-1165 (1997) and PCT Application Publication No. WO2018/213337. In some embodiments, the amino acid sequences of the entire FMC63-derived scFv (also referred to as FMC63 scFv) and its different portions are provided in Table 7 below. In some embodiments, the CD19-specific scFv comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14019, 14020, or 14025, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO:14019, 14020, or 14025. In some embodiments, the CD19-specific scFv comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14021-14023 and 14026-14028. In some embodiments, the CD19-specific scFv comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14021-14023. In some embodiments, the CD19-specific scFv comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14026-14028. In any of these embodiments, the CD19-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the CD19 CAR comprises or consists of the one or more CDRs as described herein.

In some embodiments, the linker linking the V_H and the V_L portions of the scFv is a Whitlow linker having an amino acid sequence set forth in SEQ ID NO:14024. In some embodiments, the Whitlow linker is replaced by a different linker, for example, a 3×G4S linker (SEQ ID NO: 9313) having an amino acid sequence set forth in SEQ ID NO: 14030, which gives rise to a different FMC63-derived scFv having an amino acid sequence set forth in SEQ ID NO:14029. In certain of these embodiments, the CD19-specific scFv comprises or consists of an amino acid sequence set forth in SEQ ID NO:14029 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO:14029.

TABLE 7
Exemplary sequences of anti-CD19 scFv and components

SEQ ID NO:	Amino Acid Sequence	Description
14019	DIQMTQTTSSLSASLGDRVTIS-	Anti-CD19 FMC63 scFv
	CRASQDISKY-LNWYQQKPDGT	entire sequence, with
	VKLLI-YHTSRLHSGVPSRFSG	Whitlow linker
	SGSGTDYSLTISNLEQEDIATY
	FCQQGN-TLPYTFGGGTKLEIT-
	GSTSGSGKPGSGEGSTKGEV-K
	LQESGPGLVAPSQSLSVTCTVS
	GVSLPDYGVSWIRQP-PRKGLE
	LGVIWGSET-TYYNSALKSRLT
	IIKDNSKSQVFLK-MNSLQTDD
	TAIYYCAKHYYYGGSYAMDYWG
	QGTSVTVSS
14020	DIQMTQTTSSLSASLGDRVTIS-	Anti-CD19 FMC63 scFv
	CRASQDISKY-LNWYQQKPDGTV	light chain variable
	KLLI-YHTSRLHSGVPSRFSGSG	region
	SGTDYSLTISNLEQEDIATYFCQ
	QGN-TLPYTFGGGTKLEIT
14021	QDISKY	Anti-CD19 FMC63 scFv
		light chain CDR1
	HTS	Anti-CD19 FMC63 scFv
		light chain CDR2
14023	QQGNTLPYT	Anti-CD19 FMC63 scFv
		light chain CDR3
14024	GSTSGSGKPGSGEGSTKG	Whitlow linker
14025	EVKLQESGPGLVAP-SQSLSV	Anti-CD19 FMC63 scFv
	TCTVSGVSLPDY-GVSWIRQP-	heavy chain variable
	PRKGLEWLGVIWGSET-TYYN	region
	SALKSRLTIIKDNSKSQVFLK
	MNSLQTDD-TAIYYCAKHYYY
	GGSYAMDYWGQGTSVTVSS
14026	GVSLPDYG	Anti-CD19 FMC63 scFv
		heavy chain CDR1
14027	IWGSETT	Anti-CD19 FMC63 scFv
		heavy chain CDR2
14028	AKHYYYGGSYAMDY	Anti-CD19 FMC63 scFv
		heavy chain CDR3
14029	DIQMTQTTSSLSASLGDRVTIS-	Anti-CD19 FMC63 scFv
	CRASQDISKY-LNWYQQKPDGT	entire sequence, with
	VKLLI-YHTSRLHSGVPSRFSG	3xG4S linker (SEQ ID
	SGSGTDYSLTISNLEQEDIATY	NO: 9313)
	FCQQGN-TLPYTFGGGTKLEIT-
	GGGGSGGGGSGGGGSEV-KLQE
	SGPGLVAPSQSLSVTCTVSGVS
	LPDYGVSWIRQP-PRKGLEWLG
	VIWGSET-TYYNSALKSRLTII
	KDNSKSQVFLK-MNSLQTDDTA
	IYYCAKHYYYGGSYAMDYWGQG
	TSVTVSS
14030	GGGGSGGGGSGGGGS	3xG4S linker

In some embodiments, the extracellular binding domain of the CD19 CAR is derived from an antibody specific to CD19, including, for example, SJ25C1 (Bejcek et al., Cancer Res. 55:2346-2351 (1995)), HD37 (Pezutto et al., J. Immunol. 138(9):2793-2799 (1987)), 4G7 (Meeker et al., Hybridoma 3:305-320 (1984)), B43 (Bejcek (1995)), BLY3 (Bejcek (1995)), B4 (Freedman et al., 70:418-427 (1987)), B4 HB12b (Kansas & Tedder, J. Immunol. 147:4094-4102 (1991); Yazawa et al., Proc. Natl. Acad. Sci. USA 102:15178-15183 (2005); Herbst et al., J. Pharmacol. Exp. Ther. 335:213-222 (2010)), BU12 (Callard et al., J. Immunology, 148(10):2983-2987 (1992)), and CLB-CD19 (De Rie Cell. Immunol. 118:368-381 (1989)). In any of these 10 embodiments, the extracellular binding domain of the CD19 CAR comprises or consists of the V_H, the V_L, and/or one or more CDRs of any of the antibodies.

In some embodiments, the hinge domain of the CD19 CAR comprises a CD4 hinge domain, for example, a human CD4 hinge domain. In some embodiments, the CD4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14006 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14006. In some embodiments, the hinge domain comprises a CD28 hinge domain, for example, a human CD28 hinge domain. In some embodiments, the CD28 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO:14007 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO:14007. In some embodiments, the hinge domain comprises an IgG4 hinge domain, for example, a human IgG4 hinge domain. In some embodiments, the IgG4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO:14008 or SEQ ID NO:14009, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14008 or SEQ ID NO: 14009. In some embodiments, the hinge domain comprises a IgG4 hinge-Ch2-Ch3 domain, for example, a human IgG4 hinge-Ch2-Ch3 domain. In some embodiments, the IgG4 hinge-Ch2-Ch3 domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14010 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14010.

In some embodiments, the transmembrane domain of the CD19 CAR comprises a CD4 transmembrane domain, for example, a human CD4 transmembrane domain. In some embodiments, the CD4 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14011 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14011. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain, for example, a human CD28 transmembrane domain. In some embodiments, the CD28 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14012 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14012.

In some embodiments, the intracellular costimulatory domain of the CD19 CAR comprises a 4-1BB costimulatory domain. 4-1BB, also known as CD137, transmits a potent costimulatory signal to T cells, promoting differentiation and enhancing long-term survival of T lymphocytes. In some embodiments, the 4-1BB costimulatory domain is human. In some embodiments, the 4-1BB costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14015 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14015. In some embodiments, the intracellular costimulatory domain comprises a CD28 costimulatory domain. CD28 is another co-stimulatory molecule on T cells. In some embodiments, the CD28 costimulatory domain is human. In some embodiments, the CD28 costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14016 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14016. In some embodiments, the intracellular costimulatory domain of the CD19 CAR comprises a 4-1BB costimulatory domain and a CD28 costimulatory domain as described.

In some embodiments, the intracellular signaling domain of the CD19 CAR comprises a CD3 zeta (2) signaling domain. CD37 associates with T cell receptors (TCRs) to produce a signal and contains immunoreceptor tyrosine-based activation motifs (ITAMs). The CD37 signaling domain refers to amino acid residues from the cytoplasmic domain of the zeta chain that are sufficient to functionally transmit an initial signal necessary for T cell activation. In some embodiments, the CD3ζ signaling domain is human. In some embodiments, the CD37 signaling domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14017 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14017.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD19 CAR, including, for example, a CD19 CAR comprising the CD19-specific scFv having sequences set forth in SEQ ID NO: 14019 or SEQ ID NO: 14029, the CD4 hinge domain of SEQ ID NO:14006, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD34 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof. In any of these embodiments, the CD19 CAR additionally comprises a signal peptide (e.g., a CD4 signal peptide) as described.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD19 CAR, including, for example, a CD19 CAR comprising the CD19-specific scFv having sequences set forth in SEQ ID NO: 14019 or SEQ ID NO: 14029, the IgG4 hinge domain of SEQ ID NO:14008 or SEQ ID NO: 14009, the CD28 transmembrane domain of SEQ ID NO:14012, the 4-1 BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof. In any of these embodiments, the CD19 CAR additionally comprises a signal peptide (e.g., a CD4 signal peptide) as described.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD19 CAR, including, for example, a CD19 CAR comprising the CD19-specific scFv having sequences set forth in SEQ ID NO: 14019 or SEQ ID NO: 14029, the CD28 hinge domain of SEQ ID NO: 14007, the CD28 transmembrane domain of SEQ ID NO: 14012, the CD28 costimulatory domain of SEQ ID NO: 14016, the CD33 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof. In any of these embodiments, the CD19 CAR additionally comprises a signal peptide (e.g., a CD4 signal peptide) as described.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD19 CAR as set forth in SEQ ID NO: 14031 or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence set forth in SEQ ID NO: 14031 (see Table 8). The encoded CD19 CAR has a corresponding amino acid sequence set forth in SEQ ID NO: 14032 or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14032, with the following components: CD4 signal peptide, FMC63 scFv (V_L-Whitlow linker-V_H), CD4 hinge domain, CD4 transmembrane domain, 4-1BB costimulatory domain, and CD3ζ signaling domain.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a commercially available embodiment of CD19 CAR. Non-limiting examples of commercially available embodiments of CD19 CARs expressed and/or encoded by T cells include tisagenlecleucel, lisocabtagene maraleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding tisagenlecleucel or portions thereof. Tisagenlecleucel comprises a CD19 CAR with the following components: CD4 signal peptide, FMC63 scFv (V_L-3×G4S linker-V_H), CD4 hinge domain, CD4 transmembrane domain, 4-1BB costimulatory domain, and CD37 signaling domain. The nucleotide and amino acid sequence of the CD19 CAR in tisagenlecleucel are provided in Table 8, with annotations of the sequences provided in Table 9.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding lisocabtagene maraleucel or portions thereof. Lisocabtagene maraleucel comprises a CD19 CAR with the following components: GMCSFR-α or CSF2RA signal peptide, FMC63 scFv (V_L-Whitlow linker-V_H), IgG4 hinge domain, CD28 transmembrane domain, 4-1BB costimulatory domain, and CD37 signaling domain. The nucleotide and amino acid sequence of the CD19 CAR in lisocabtagene maraleucel are provided in Table 8, with annotations of the sequences provided in Table 10.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding axicabtagene ciloleucel or portions thereof. Axicabtagene ciloleucel comprises a CD19 CAR with the following components: GMCSFR-α or CSF2RA signal peptide, FMC63 scFv (V_L-Whitlow linker-V_H), CD28 hinge domain, CD28 transmembrane domain, CD28 costimulatory domain, and CD33 signaling domain. The nucleotide and amino acid sequence of the CD19 CAR in axicabtagene ciloleucel are provided in Table 8, with annotations of the sequences provided in Table 11.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding brexucabtagene autoleucel or portions thereof. Brexucabtagene autoleucel comprises a CD19 CAR with the following components: GMCSFR-α signal peptide, FMC63 scFv, CD28 hinge domain, CD28 transmembrane domain, CD28 costimulatory domain, and CD3ζ signaling domain.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD19 CAR as set forth in SEQ ID NO: 14033, 14035, or 14037, or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence set forth in SEQ ID NO: 14033, 14035, or 14037. The encoded CD19 CAR has a corresponding amino acid sequence set forth in SEQ ID NO: 14034, 14036, or 14038, respectively, or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14034, 14036, or 14038, respectively.

TABLE 8
Exemplary sequences of CD19 CARs

SEQ ID NO:	Sequence	Description
14031	atggccttaccagtgaccgccttgctcctgccgct	Exemplary CD19
	ggcctt-gctgctccac-gccgccaggccggacat	CAR nucleotide
	ccagatgacacagactacatcctccctgtctgcct	sequence
	ctctgggagacagagtcaccatcagtt-gcagggc
	aagtcaggacatt-agtaaatatttaaattggtat
	cagcagaaaccagatggaactgttaaactcctgat
	ctaccatacatcaagattacactcag-gagtccca
	tcaaggttcag-tggcagtgggtctggaacagatt
	attctctcaccattagcaacctggagcaagaagat
	attgccacttactttt-gccaacagggtaatacgc
	ttccgtacac-gttcggaggggggaccaagctgga
	gatcacaggctccacctctggatccggcaagcccg
	-gatctggcgagggatccaccaagggcgaggtgaa
	actg-cag-gagtcaggacctggcctggtggcgcc
	ctcacagagcctgtccgtcacatgcactgtctcag
	gggtctcattacccgac-tatggtgtaagctggat
	-tcgccagcctccacgaaagggtctggagtggctg
	ggagtaatatggggtagtgaaaccacatacta-ta
	attcagctctcaaatccagactgac-catcatcaa
	ggacaactccaagagccaagttttcttaaaaatga
	acagtctg-caaactgatgacacagccatttacta
	ctgtgccaaacattattactacggtggtagctatg
	ctatggac-tactggggccaaggaacctcagtcac
	-cgtctcctcaaccacgacgccagcgccgcgacca
	ccaacaccggcgcccaccatcgcgtcg-cagcccc
	tgtccctgcgcccagaggcgtgccggccagcggcg
	gggggcgcagtgcacacgagggggctg-gacttcg
	cctgtga-tatctacatctgggcgcccttggccgg
	gacttgtggggtccttctcctgtcactggttatca
	ccctttactgcaaacgggg-cagaaagaaactcct
	gtata-tattcaaacaaccatttatgagaccagta
	caaactactcaagaggaagatggctgtagctgccg
	atttccagaagaa-gaagaaggaggatgtgaactg
	agag-tgaagttcagcaggagcgcagacgcccccg
	cgtaccagcagggccagaaccagctctataacgag
	ctcaatctag-gacgaagagaggagtacgatgttt
	t-ggacaagagacgtggccgggaccctgagatggg
	gggaaagccgagaaggaagaaccctcaggaaggcc
	tg-tacaatgaactgcagaaagataa-gatggcgg
	aggcctacagtgagattgggatgaaaggcgagcgc
	cggaggggcaaggggcacgatggcctttac-cagg
	gtctcagtacagccac-caaggacacctacgacgc
	ccttcacatgcaggccctgccccctcgc
14032	MAL-PVTALLLPLALLLHAARPDIQMTQTTSSLSA	Exemplary CD19
	SLGDRVTISCRASQDISKY-LNWYQQKPDGTVKLL	CAR amino acid
	I-YHTSRLHSGVPSRFSGSGSGTDYS-LTISNLEQ	sequence
	EDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGK
	PGSGEGSTKGEV-KLQESGPGLVAP-SQSLSVTCT
	VSGVSLPDY-GVSWIRQPPRKGLEWLGVIWGSETT
	YYNSALKSRLTIIKDNSKSQVFLKMNSLQTDD-TA
	IYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAP
	RPPTPAPTI-ASQPLSLRPEACRPAAGGAVHTRGL
	D-FACDIYIWAPLAG-TCGVLLLSLVITLYCKRGR
	KKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEE-G
	GCELRVKFSRSADAPA-YQQGQNQLYNELNLGR-R
	EEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL-Q
	KDKMAEAYSEIGMKGERRRGKGH-DGLYQGLSTAT
	KDTYDALHMQALPPR
14033	atggccttaccagtgaccgccttgctcctgccgct	Tisagenlecleucel
	ggcctt-gctgctccac-gccgccaggccggacat	CD19 CAR
	ccagatgacacagactacatcctccctgtctgcct	nucleotide
	ctctgggagacagagtcaccatcagtt-gcagggc	sequence
	aagtcaggacatt-agtaaatatttaaattggtat
	cagcagaaaccagatggaactgttaaactcctgat
	ctaccatacatcaagattacactcag-gagtccca
	tcaaggttcag-tggcagtgggtctggaacagatt
	attctctcaccattagcaacctggagcaagaagat
	attgccacttactttt-gccaacagggtaatacgc
	ttccgtacac-gttcggaggggggaccaagctgga
	gatcacaggtggcggtggctcgggcggtggtgggt
	cgggtggcggcg-gatctgaggtgaaactgcagga
	gtcag-gacctggcctggtggcgccctcacagagc
	ctgtccgtcacatgcactgtctcaggggtctcatt
	acccgactatggtgtaa-gctggattcgccagcct
	ccac-gaaagggtctggagtggctgggagtaatat
	ggggtagtgaaaccacatactataattcagctctc
	aaatccagactgac-catcatcaaggacaactcca
	a-gagccaagttttcttaaaaatgaacagtctgca
	aactgatgacacagccatttactactgtgccaaac
	attattactac-ggtggtagctatgctatggac-t
	actggggccaaggaacctcagtcaccgtctcctca
	accacgacgccagcgccgcgaccaccaacac-cgg
	cgcccaccatcgcgtcg-cagcccctgtccctgcg
	cccagaggcgtgccggccagcggcggggggcgcag
	tgcacacgagggggctg-gacttcgcctgtga-ta
	tctacatctgggcgcccttggccgggacttgtggg
	gtccttctcctgtcactggttatcaccctttactg
	caaacgggg-cagaaagaaactcctgtata-tatt
	caaacaaccatttatgagaccagtacaaactactc
	aagaggaagatggctgtagctgccgatttccagaa
	gaa-gaagaaggaggatgtgaactgagag-tgaag
	ttcagcaggagcgcagacgcccccgcgtacaagca
	gggccagaaccagctctataacgagctcaatctag
	-gacgaagagaggagtacgatgtttt-ggacaaga
	gacgtggccgggaccctgagatggggggaaagccg
	agaaggaagaaccctcaggaaggcctg-tacaatg
	aactgcagaaagataa-gatggcggaggcctacag
	tgagattgggatgaaaggcgagcgccggaggggca
	aggggcacgatggcctttac-cagggtctcagtac
	agccac-caaggacacctacgacgcccttcacatg
	caggccctgccccctcgc
14034	MAL-PVTALLLPLALLLHAARPDIQMTQTTSSLSA	Tisagenlecleucel
	SLGDRVTISCRASQDISKY-LNWYQQKPDGTVKLL	CD19 CAR
	I-YHTSRLHSGVPSRFSGSGSGTDYS-LTISNLEQ	amino acid
	EDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGG	sequence
	GSGGGGSEV-KLQESGPGLVAP-SQSLSVTCTVSG
	VSLPDYGVSWIRQP-PRKGLEWLGVIWGSETTYYN
	SALKSRLTIIKDNSKSQVFLKMNSLQTDD-TAIYY
	CAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPP
	TPAPTI-ASQPLSLRPEACRPAAGGAVHTRGLD-F
	ACDIYIWAPLAG-TCGVLLLSLVITLYCKRGRKKL
	LYIFKQPFMRPVQTTQEEDGCSCRFPEEEE-GGCE
	LRVKFSRSADAPA-YKQGQNQLYNELNLGR-REEY
	DVLDKRRGRDPEMGGKPRRKNPQEGLYNEL-QKDK
	MAEAYSEIGMKGERRRGKGH-DGLYQGLSTATKDT
	YDALHMQALPPR
14035	atgctgctgctggtgac-cagcctgctgctgtgcg	Lisocabtagene
	agctgccccaccccgcctttctgctgatccccgac	maraleucel
	atccagatgacccagaccac-ctccagcctgagcg	CD19 CAR nucleotide
	ccagcctgggcgac-cgggtgaccatcagctgccg	sequence
	ggccagccaggacatcagcaagtacctgaactggt
	atcagcagaagcccgacgg-caccgtcaagctgct
	gatctac-cacaccagccggctgcacagcggcgtg
	cccagccggtttagcggcagcggctccggcaccga
	ctacagcctgac-catctccaacctggaacaggaa
	ga-tatcgccacctacttttgccagcagggcaaca
	cactgccctacacctttggcggcggaacaaagctg
	gaaatcaccgg-cagcacctccggcagcggcaa-g
	cctggcagcggcgagggcagcaccaagggcgaggt
	gaagctgcaggaaa-gcggccctggcctggtggcc
	cccagccagagcctgagcgtgacctgcaccgtgag
	cggcgtgagcctgcccgactac-ggcgtgagctgg
	atccgg-cagccccccaggaagggcctggaatggc
	tgggcgtgatctggggcagcgagaccacctactac
	aacagcgccctgaa-gagccggctgac-catcatc
	aaggacaacagcaagagccaggtgttcctgaagat
	gaacagcctgcagaccgacgacac-cgccatctac
	tactgcgccaagcactactactac-ggcggcagct
	acgccatggactactggggccagggcaccagcgtg
	accgtgagcagcgaatctaagtacggac-cgccct
	gcccccctt-gccctatgttctgggtgctggtggt
	ggtcggaggcgtgctggcctgctacagcctgctgg
	tcaccgtggccttcatcatctttt-gggtgaaacg
	gggcagaaa-gaaactcctgtatatattcaaacaa
	ccatttatgagaccagtacaaactactcaagagga
	agatggctgtagctgccgat-ttccagaagaagaa
	gaaggag-gatgtgaactgcgggtgaagttcagca
	gaagcgccgacgcccctgcctaccagcagggccag
	aatcagctgtacaac-gagctgaacctgggcagaa
	gggaa-gagtacgacgtcctggataagcggagagg
	ccgggaccctgagatgggcggcaagcctcggcgga
	agaacccccag-gaaggcctgtataacgaactg-c
	agaaagacaagatggccgaggcctacagcgagatc
	ggcatgaagggcgagcggaggcggggcaagggcca
	c-gacggcctgtatcagggcctgtccac-cgccac
	caaggatacctacgacgccctgcacatgcaggccc
	tgcccccaagg
14036	MLLLVTSLLLCELPHPAFL-LIPDIQMTQTTSSLS	Lisocabtagene
	ASLGDRVTIS-CRASQDISKY-LNWYQQKPDGTVK	maraleucel
	LLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQ	CD19 CAR
	EDIATY-FCQQGNTLPYTFGGGTKLEIT-GSTSGS	amino acid
	GKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCT	sequence
	VSGVSLPDY-GVSWIRQPPRKGLEWLGVIWGSET-
	TYYNSALKSRLTIIK-DNSKSQVFLKMNSLQTDDT
	AIYYCAKHYYYGGSYAMDYWGQGTSVTVSSESKYG
	PPCPPCPMFWVLVVVGGVLACYSLLVTVAFI-IFW
	VKRGRKKLLY-IFKQPFMRPVQTTQEEDGCSCRFP
	EEEEGGCELRVKFSRSADAPA-YQQGQNQLYNELN
	LGR-REEYDVLDKRRGRDPEMGGKPRR-KNPQEGL
	YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGL
	STAT-KDTYDALHMQALPPR
14037	atgcttctcctggtgacaagccttctgctctgtga	Axicabtagene ci-
	gttac-cacacccag-cattcctcctgatcccaga	loleucel CD19
	catccagatgacacagactacatcctccctgtctg	CAR nucleotide
	cctctctgggagacagagtcac-catcagttgcag	sequence
	ggcaagtcag-gacattagtaaatatttaaattgg
	tatcagcagaaaccagatggaactgttaaactcct
	gatctaccatacatcaagat-tacactcaggag-t
	cccatcaaggttcagtggcagtgggtctggaacag
	attattctctcaccattagcaacctggagcaagaa
	gatattgccac-ttacttttgccaacagggtaa-t
	acgcttccgtacacgttcggaggggggactaagtt
	ggaaataacaggctccacctctggatccggcaagc
	ccg-gatctggcgagggatccac-caagggcgagg
	tgaaactgcaggagtcaggacctggcctggtggcg
	ccctcacagagcctgtccgtcacatgcac-tgtct
	caggggtctcattacccgac-tatggtgtaagctg
	gattcgccagcctccacgaaagggtctggagtggc
	tgggagtaatatggggtagtgaaac-cacatacta
	-taattcagctctcaaatccagactgaccatcatc
	aaggacaactccaagagccaagttttcttaaaaat
	gaacagtctg-caaactgatgacacagccatttac
	tactgtgccaaacattattactacggtggtagcta
	tgctatggac-tactggggtcaaggaacctcagtc
	ac-cgtctcctcagcggccgcaattgaagttatgt
	atcctcctccttacctagacaatgagaagagcaat
	ggaac-cattatccatgtgaaagggaaacaccttt
	-gtccaagtcccctatttcccggaccttctaagcc
	cttttgggtgctggtggtggttgggggagtcctgg
	cttgctatagctt-gctagtaacag-tggccttta
	ttattttctgggtgaggagtaagaggagcaggctc
	ctgcacagtgac-tacatgaacatgactccccgcc
	gccccgggcccacccg-caagcattac-cagccct
	atgccccaccacgcgacttcgcagcctatcgctcc
	agagtgaagttcagcaggagcgcagac-gcccccg
	cgtaccagcagggccagaaccagctc-tataacga
	gctcaatctaggacgaagagaggagtacgatgttt
	tggacaagagacgtggccgggaccctga-gatggg
	gggaaagccgagaaggaa-gaaccctcaggaaggc
	ctgtacaatgaactgcagaaagataagatggcgga
	ggcctacagtgagattgg-gatgaaaggcgagcgc
	cggaggggcaagggg-cacgatggcctttaccagg
	gtctcagtacagccaccaaggacacctacgac-gc
	ccttcacatgcaggccctgccccctcgc
14038	MLLLVTSLLLCELPHPAFL-LIPDIQMTQTTSSLS	Axicabtagene ci-
	ASLGDRVTIS-CRASQDISKY-LNWYQQKPDGTVK	loleucel CD19
	LLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQ	CAR amino acid
	EDIATY-FCQQGNTLPYTFGGGTKLEIT-GSTSGS	sequence
	GKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCT
	VSGVSLPDY-GVSWIRQPPRKGLEWLGVIWGSET-
	TYYNSALKSRLTIIK-DNSKSQVFLKMNSLQTDDT
	AIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAAIE
	VMYPPPYLDNEKSNGTIIHVKGKHLCPSPLF-PGP
	SKPFWVLVVVGGVLACYSLLVTVAFII-FWVRSKR
	SRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAY
	RSRVKFSRSADAPA-YQQGQNQLYNELNLGR-REE
	YDVLDKRRGRD-PEMGGKPRRKNPQEGLYNELQKD
	KMAEAYSEIGMKGERRRGKGHDGLYQGLSTAT-KD
	TYDALHMQALPPR

TABLE 9
Annotation of tisagenlecleucel CD19 CAR sequences

	Nucleotide	Amino Acid
Feature	Sequence Position	Sequence Position
CD8a signal peptide	1-63	1-21
FMC63 scFv	64-789	22-263
(VL-3xG4S linker-VH)
CD8α hinge domain	790-924	264-308
CD8α transmembrane domain	925-996	309-332
4-1BB costimulatory domain	997-1122	333-374
CD3ζ signaling domain	1123-1458	375-486

TABLE 10
Annotation of lisocabtagene maraleucel CD19 CAR sequences

	Nucleotide	Amino Acid
Feature	Sequence Position	Sequence Position
GMCSFR-a signal peptide	1-66	1-22
FMC63 scFv	67-801	23-267
(VL-Whitlow linker-VH)
IgG4 hinge domain	802-837	268-279
CD28 transmembrane domain	838-921	280-307
4-1BB costimulatory domain	922-1047	308-349
CD3ζ signaling domain	1048-1383	350-461

TABLE 11
Annotation of axicabtagene ciloleucel CD19 CAR sequences

	Nucleotide	Amino Acid
Feature	Sequence Position	Sequence Position
CSF2RA signal peptide	1-66	1-22
FMC63 scFv	67-801	23-267
(VL-Whitlow linker-VH)
CD28 hinge domain	802-927	268-309
CD28 transmembrane domain	928-1008	310-336
CD28 costimulatory domain	1009-1131	337-377
CD3ζ signaling domain	1132-1467	378-489

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding CD19 CAR as set forth in SEQ ID NO: 14033, 14035, or 14037, or at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence set forth in SEQ ID NO: 14033, 14035, or 14037. The encoded CD19 CAR has a corresponding amino acid sequence set forth in SEQ ID NO: 14034, 14036, or 14038, respectively, or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14034, 14036, or 14038, respectively.

CD20 CAR

In some embodiments, the CAR is a CD20 CAR (“CD20-CAR”), and in these embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR. CD20 is an antigen found on the surface of B cells as early at the pro-B phase and progressively at increasing levels until B cell maturity, as well as on the cells of most B-cell neoplasms. CD20 positive cells are also sometimes found in cases of Hodgkins disease, myeloma, and thymoma. In some embodiments, the CD20 CAR comprises a signal peptide, an extracellular binding domain that specifically binds CD20, a hinge domain, a transmembrane domain, an intracellular costimulatory domain, and/or an intracellular signaling domain in tandem.

In some embodiments, the signal peptide of the CD20 CAR comprises a CD4 signal peptide. In some embodiments, the CD4 signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO:14003 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO:14003. In some embodiments, the signal peptide comprises an IgK signal peptide. In some embodiments, the IgK signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14004 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14004. In some embodiments, the signal peptide comprises a GMCSFR-α or CSF2RA signal peptide. In some embodiments, the GMCSFR-α or CSF2RA signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14005 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14005.

In some embodiments, the extracellular binding domain of the CD20 CAR is specific to CD20, for example, human CD20. The extracellular binding domain of the CD20 CAR is codon-optimized for expression in a host cell or to have variant sequences to increase functions of the extracellular binding domain. In some embodiments, the extracellular binding domain comprises an immunogenically active portion of an immunoglobulin molecule, for example, an scFv.

In some embodiments, the extracellular binding domain of the CD20 CAR is derived from an antibody specific to CD20, including, for example, Leu16, IF5, 1.5.3, rituximab, obinutuzumab, ibritumomab, ofatumumab, tositumumab, odronextamab, veltuzumab, ublituximab, and ocrelizumab. In any of these embodiments, the extracellular binding domain of the CD20 CAR comprises or consists of the V_H, the V_L, and/or one or more CDRs of any of the antibodies.

In some embodiments, the extracellular binding domain of the CD20 CAR comprises an scFv derived from the Leu16 monoclonal antibody, which comprises the heavy chain variable region (V_H) and the light chain variable region (V_L) of Leu16 connected by a linker. See Wu et al., Protein Engineering. 14(12):1025-1033 (2001). In some embodiments, the linker is a 3×G4S linker (SEQ ID NO: 9313). In other embodiments, the linker is a Whitlow linker as described herein. In some embodiments, the amino acid sequences of different portions of the entire Leu16-derived scFv (also referred to as Leu16 scFv) and its different portions are provided in Table 12 below. In some embodiments, the CD20-specific scFv comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14039, 14040, or 14044, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14039, 14040, or 14044. In some embodiments, the CD20-specific scFv comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14041-14043, 14045 and 14046. In some embodiments, the CD20-specific scFv comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14041-14043. In some embodiments, the CD20-specific scFv comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14045-14046. In any of these embodiments, the CD20-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the CD20 CAR comprises or consists of the one or more CDRs as described herein.

TABLE 12
Exemplary sequences of anti-CD20 scFv and components

SEQ ID NO:	Amino Acid Sequence	Description
14039	DIVLTQSPAILSASPGEKVTMT-	Anti-CD20 Leu16 scFv
	CRASSSVNYMDWYQKKPGSSPKP-	entire sequence, with
	WIYATSNLAS-	Whitlow linker
	GVPARFSGSGSGTSYSLTISRVEAE
	DAATYYCQQWS-
	FNPPTFGGGTKLEIKGSTSGSGKP
	GSGEGSTKGEVQLQQSGAELVKP-
	GASVKMSCKASGYTFTSYN-
	MHWVKQTPGQGLEWIGAI-
	YPGNGDTSYNQKFKGKATLTADKS
	SSTAYMQLSSLTSED-
	SADYYCARSNYYGSSYWFFDVW-
	GAGTTVTVSS
14040	DIVLTQSPAILSASPGEKVTMT-	Anti-CD20 Leu16 scFv
	CRASSSVNYMDWYQKKPGSSPKP-	light chain variable
	WIYATSNLAS-	region
	GVPARFSGSGSGTSYSLTISRVEAE
	DAATYYCQQWS-
	FNPPTFGGGTKLEIK
14041	RASSSVNYMD	Anti-CD20 Leu16 scFv
		light chain CDR1
14042	ATSNLAS	Anti-CD20 Leu16 scFv
		light chain CDR2
14043	QQWSFNPPT	Anti-CD20 Leu16 scFv
		light chain CDR3
14044	EVQLQQSGAELVKPGASVKMSCK-	Anti-CD20 Leu16 scFv
	ASGYTFTSYN-	heavy chain
	MHWVKQTPGQGLEWIGAIYPGNG-
	DTSYNQKFKGKATLTADKSSSTAY
	MQLSSLTSED-
	SADYYCARSNYYGSSYWFFDVW-
	GAGTTVTVSS
14045	SYNMH	Anti-CD20 Leu16 scFv
		heavy chain CDR1
14046	AIYPGNGDTSYNQKFKG	Anti-CD20 Leu16 scFv
		heavy chain CDR2

In some embodiments, the hinge domain of the CD20 CAR comprises a CD4 hinge domain, for example, a human CD4 hinge domain. In some embodiments, the CD4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14006 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14006. In some embodiments, the hinge domain comprises a CD28 hinge domain, for example, a human CD28 hinge domain. In some embodiments, the CD28 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14007 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14007. In some embodiments, the hinge domain comprises an IgG4 hinge domain, for example, a human IgG4 hinge domain. In some embodiments, the IgG4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14008 or SEQ ID NO: 14009, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14008 or SEQ ID NO: 14009. In some embodiments, the hinge domain comprises a IgG4 hinge-Ch2-Ch3 domain, for example, a human IgG4 hinge-Ch2-Ch3 domain. In some embodiments, the IgG4 hinge-Ch2-Ch3 domain comprises or consists of an amino acid sequence set forth in SEQ ID NO:14010 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14010.

In some embodiments, the transmembrane domain of the CD20 CAR comprises a CD4 transmembrane domain, for example, a human CD4 transmembrane domain. In some embodiments, the CD4 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14011 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14011. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain, for example, a human CD28 transmembrane domain. In some embodiments, the CD28 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14012 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14012.

In some embodiments, the intracellular costimulatory domain of the CD20 CAR comprises a 4-1BB costimulatory domain, for example, a human 4-1BB costimulatory domain. In some embodiments, the 4-1BB costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14015 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14015. In some embodiments, the intracellular costimulatory domain comprises a CD28 costimulatory domain, for example, a human CD28 costimulatory domain. In some embodiments, the CD28 costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14016 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14016.

In some embodiments, the intracellular signaling domain of the CD20 CAR comprises a CD3 zeta (2) signaling domain, for example, a human CD3ζ signaling domain. In some embodiments, the CD32 signaling domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14017 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14017.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR, including, for example, a CD20 CAR comprising the CD20-specific scFv having sequences set forth in SEQ ID NO: 14039, the CD4 hinge domain of SEQ ID NO: 14006, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD3ζ signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR, including, for example, a CD20 CAR comprising the CD20-specific scFv having sequences set forth in SEQ ID NO: 14039, the CD28 hinge domain of SEQ ID NO: 14007, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR, including, for example, a CD20 CAR comprising the CD20-specific scFv having sequences set forth in SEQ ID NO: 14039, the IgG4 hinge domain of SEQ ID NO: 14008 or SEQ ID NO: 14009, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR, including, for example, a CD20 CAR comprising the CD20-specific scFv having sequences set forth in SEQ ID NO: 14039, the CD4 hinge domain of SEQ ID NO: 14006, the CD28 transmembrane domain of SEQ ID NO: 14012, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD34 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR, including, for example, a CD20 CAR comprising the CD20-specific scFv having sequences set forth in SEQ ID NO: 14039, the CD28 hinge domain of SEQ ID NO: 14007, the CD28 transmembrane domain of SEQ ID NO: 14012, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD20 CAR, including, for example, a CD20 CAR comprising the CD20-specific scFv having sequences set forth in SEQ ID NO: 14039, the IgG4 hinge domain of SEQ ID NO: 14008 or SEQ ID NO: 14009, the CD28 transmembrane domain of SEQ ID NO: 14012, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD34 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

CD22 CAR

In some embodiments, the CAR is a CD22 CAR (“CD22-CAR”), and in these embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR. CD22, which is a transmembrane protein found mostly on the surface of mature B cells that functions as an inhibitory receptor for B cell receptor (BCR) signaling. CD22 is expressed in 60-70% of B cell lymphomas and leukemias (e.g., B-chronic lymphocytic leukemia, hairy cell leukemia, acute lymphocytic leukemia (ALL), and Burkitt's lymphoma) and is not present on the cell surface in early stages of B cell development or on stem cells. In some embodiments, the CD22 CAR comprises a signal peptide, an extracellular binding domain that specifically binds CD22, a hinge domain, a transmembrane domain, an intracellular costimulatory domain, and/or an intracellular signaling domain in tandem.

In some embodiments, the signal peptide of the CD22 CAR comprises a CD4 signal peptide. In some embodiments, the CD4 signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14003 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14003. In some embodiments, the signal peptide comprises an IgK signal peptide. In some embodiments, the IgK signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14004 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14004. In some embodiments, the signal peptide comprises a GMCSFR-α or CSF2RA signal peptide. In some embodiments, the GMCSFR-α or CSF2RA signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14005 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14005.

In some embodiments, the extracellular binding domain of the CD22 CAR is specific to CD22, for example, human CD22. The extracellular binding domain of the CD22 CAR is codon-optimized for expression in a host cell or to have variant sequences to increase functions of the extracellular binding domain. In some embodiments, the extracellular binding domain comprises an immunogenically active portion of an immunoglobulin molecule, for example, an scFv.

In some embodiments, the extracellular binding domain of the CD22 CAR is derived from an antibody specific to CD22, including, for example, SM03, inotuzumab, epratuzumab, moxetumomab, and pinatuzumab. In any of these embodiments, the extracellular binding domain of the CD22 CAR comprises or consists of the V_H, the V_L, and/or one or more CDRs of any of the antibodies.

In some embodiments, the extracellular binding domain of the CD22 CAR comprises an scFv derived from the m971 monoclonal antibody (m971), which comprises the heavy chain variable region (V_H) and the light chain variable region (V_L) of m971 connected by a linker. In some embodiments, the linker is a 3×G4S linker (SEQ ID NO: 9313). In other embodiments, the Whitlow linker is used instead. In some embodiments, the amino acid sequences of the entire m971-derived scFv (also referred to as m971 scFv) and its different portions are provided in Table 13 below. In some embodiments, the CD22-specific scFv comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14047, 14048, or 14052, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14047, 14048, or 14052. In some embodiments, the CD22-specific scFv comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14049-14051 and 14053-14055. In some embodiments, the CD22-specific scFv comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14049-14051. In some embodiments, the CD22-specific scFv comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14053-14055. In any of these embodiments, the CD22-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the CD22 CAR comprises or consists of the one or more CDRs as described herein.

In some embodiments, the extracellular binding domain of the CD22 CAR comprises an scFv derived from m971-L7, which is an affinity matured variant of m971 with significantly improved CD22 binding affinity compared to the parental antibody m971 (improved from about 2 nM to less than 50 pM). In some embodiments, the scFv derived from m971-L7 comprises the V_H and the V_L of m971-L7 connected by a 3×G4S linker (SEQ ID NO: 9313). In other embodiments, the Whitlow linker is used instead. In some embodiments, the amino acid sequences of the entire m971-L7-derived scFv (also referred to as m971-L7 scFv) and its different portions are provided in Table K below. In some embodiments, the CD22-specific scFv comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14056, 14057, or 14061, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14056, 14057, or 14061. In some embodiments, the CD22-specific scFv comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14058-14060 and 14062-14064. In some embodiments, the CD22-specific scFv comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14058-14060. In some embodiments, the CD22-specific scFv comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14062-14064. In any of these embodiments, the CD22-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the CD22 CAR comprises or consists of the one or more CDRs as described herein.

TABLE 13
Exemplary sequences of anti-CD22 scFv and components

SEQ ID NO:	Amino Acid Sequence	Description
14047	QVQLQQSGPGLVKP-	Anti-CD22 m971 scFv
	SQTLSLTCAISGDSVSS-	entire sequence, with
	NSAAWNWIRQSPSR-	3xG4S linker (SEQ ID
	GLEWLGRTYYRSKWYNDYAVSVK	NO: 9313)
	SRITINPDTSKNQFSLQLNSVTPED-
	TAVYYCAREVTGDLEDAFD-
	IWGQGTMVTVSSGGGGSGGGGSG
	GGGSDIQMTQSPSSLSASVG-
	DRVTITCRASQTI-
	WSYLNWYQQRPGKAPNLLIYAAS-
	SLQSGVPSRFSGRGSGTDFTLTISS
	LQAEDFA-
	TYYCQQSYSIPQTFGQGTKLEIK
14048	QVQLQQSGPGLVKP-	Anti-CD22 m971 scFv
	SQTLSLTCAISGDSVSS-	heavy chain variable
	NSAAWNWIRQSPSR-	region
	GLEWLGRTYYRSKWYNDYAVSVK
	SRITINPDTSKNQFSLQLNSVTPED-
	TAVYYCAREVTGDLEDAFD-
	IWGQGTMVTVSS
14049	GDSVSSNSAA	Anti-CD22 m971 scFv
		heavy chain CDR1
14050	TYYRSKWYN	Anti-CD22 m971 scFv
		heavy chain CDR2
14051	AREVTGDLEDAFDI	Anti-CD22 m971 scFv
		heavy chain CDR3
14052	DIQMTQSPSSLSASVG-	Anti-CD22 m971 scFv
	DRVTITCRASQTI-	light chain
	WSYLNWYQQRPGKAPNLLIYAAS-
	SLQSGVPSRFSGRGSGTDFTLTISS
	LQAEDFA-
	TYYCQQSYSIPQTFGQGTKLEIK
14053	QTIWSY	Anti-CD22 m971 scFv
		light chain CDR1
	AAS	Anti-CD22 m971 scFv
		light chain CDR2
14055	QQSYSIPQT	Anti-CD22 m971 scFv
		light chain CDR3
14056	QVQLQQSGPGMVKP-	Anti-CD22 m971-L7
	SQTLSLTCAISGDSVSS-	scFv entire sequence,
	NSVAWNWIRQSPSR-	with 3xG4S linker
	GLEWLGRTYYRST-	(SEQ ID NO: 9313)
	WYNDYAVSMKSRITINPDTNKNQFS
	LQLNSVTPEDTAVYYCAREV-
	TGDLEDAFD-
	IWGQGTMVTVSSGGGGSGGGGSG
	GGGSDIQMIQSPSSLSASVG-
	DRVTITCRASQTI-
	WSYLNWYRQRPGEAPNLLIYAAS-
	SLQSGVPSRFSGRGSGTDFTLTISS
	LQAEDFA-
	TYYCQQSYSIPQTFGQGTKLEIK
14057	QVQLQQSGPGMVKP-	Anti-CD22 m971-L7
	SQTLSLTCAISGDSVSS-	scFv heavy chain vari-
	NSVAWNWIRQSPSR-	able region
	GLEWLGRTYYRST-
	WYNDYAVSMKSRITINPDTNKNQFS
	LQLNSVTPEDTAVYYCAREV-
	TGDLEDAFDIWGQGTMVTVSS
14058	GDSVSSNSVA	Anti-CD22 m971-L7
		scFv heavy chain
		CDR1
14059	TYYRSTWYN	Anti-CD22 m971-L7
		scFv heavy chain
		CDR2
14060	AREVTGDLEDAFDI	Anti-CD22 m971-L7
		scFv heavy chain
		CDR3
14061	DIQMIQSPSSLSASVG-	Anti-CD22 m971-L7
	DRVTITCRASQTI-	scFv light chain varia-
	WSYLNWYRQRPGEAPNLLIYAAS-	ble region
	SLQSGVPSRFSGRGSGTDFTLTISS
	LQAEDFA-
	TYYCQQSYSIPQTFGQGTKLEIK
14062	QTIWSY	Anti-CD22 m971-L7
		scFv light chain CDR1
	AAS	Anti-CD22 m971-L7
		scFv light chain CDR2
14064	QQSYSIPQT	Anti-CD22 m971-L7
		scFv light chain CDR3

In some embodiments, the extracellular binding domain of the CD22 CAR comprises immunotoxins HA22 or BL22. Immunotoxins BL22 and HA22 are therapeutic agents that comprise an scFv specific for CD22 fused to a bacterial toxin, and thus can bind to the surface of the cancer cells that express CD22 and kill the cancer cells. BL22 comprises a dsFv of an anti-CD22 antibody, RFB4, fused to a 38-kDa truncated form of Pseudomonas exotoxin A (Bang et al., Clin. Cancer Res., 11:1545-50 (2005)). HA22 (CAT8015, moxetumomab pasudotox) is a mutated, higher affinity version of BL22 (Ho et al., J. Biol. Chem., 280(1): 607-17 (2005)). Suitable sequences of antigen binding domains of HA22 and BL22 specific to CD22 are disclosed in, for example, U.S. Pat. Nos. 7,541,034; 7,355,012; and 7,982,011.

In some embodiments, the hinge domain of the CD22 CAR comprises a CD4 hinge domain, for example, a human CD4 hinge domain. In some embodiments, the CD4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14006 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14006. In some embodiments, the hinge domain comprises a CD28 hinge domain, for example, a human CD28 hinge domain. In some embodiments, the CD28 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14007 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14007. In some embodiments, the hinge domain comprises an IgG4 hinge domain, for example, a human IgG4 hinge domain. In some embodiments, the IgG4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14008 or SEQ ID NO: 14009, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14008 or SEQ ID NO: 14009. In some embodiments, the hinge domain comprises a IgG4 hinge-Ch2-Ch3 domain, for example, a human IgG4 hinge-Ch2-Ch3 domain. In some embodiments, the IgG4 hinge-Ch2-Ch3 domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14010 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14010.

In some embodiments, the transmembrane domain of the CD22 CAR comprises a CD4 transmembrane domain, for example, a human CD4 transmembrane domain. In some embodiments, the CD4 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14011 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14011. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain, for example, a human CD28 transmembrane domain. In some embodiments, the CD28 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO:14012 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14012.

In some embodiments, the intracellular costimulatory domain of the CD22 CAR comprises a 4-1BB costimulatory domain, for example, a human 4-1BB costimulatory domain. In some embodiments, the 4-1BB costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14015 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14015. In some embodiments, the intracellular costimulatory domain comprises a CD28 costimulatory domain, for example, a human CD28 costimulatory domain. In some embodiments, the CD28 costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14016 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14016.

In some embodiments, the intracellular signaling domain of the CD22 CAR comprises a CD3 zeta (2) signaling domain, for example, a human CD37 signaling domain. In some embodiments, the CD34 signaling domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14017 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14017.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR, including, for example, a CD22 CAR comprising the CD22-specific scFv having sequences set forth in SEQ ID NO: 14047 or SEQ ID NO: 14056, the CD4 hinge domain of SEQ ID NO:9, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR, including, for example, a CD22 CAR comprising the CD22-specific scFv having sequences set forth in SEQ ID NO: 14047 or SEQ ID NO: 14056, the CD28 hinge domain of SEQ ID NO: 14007, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR, including, for example, a CD22 CAR comprising the CD22-specific scFv having sequences set forth in SEQ ID NO: 14047 or SEQ ID NO: 14056, the IgG4 hinge domain of SEQ ID NO: 14008 or SEQ ID NO: 14009, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD33 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR, including, for example, a CD22 CAR comprising the CD22-specific scFv having sequences set forth in SEQ ID NO: 14047 or SEQ ID NO: 14056, the CD4 hinge domain of SEQ ID NO:9, the CD28 transmembrane domain of SEQ ID NO: 14012, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR, including, for example, a CD22 CAR comprising the CD22-specific scFv having sequences set forth in SEQ ID NO: 14047 or SEQ ID NO: 14056, the CD28 hinge domain of SEQ ID NO: 14007, the CD28 transmembrane domain of SEQ ID NO: 14012, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD37 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a CD22 CAR, including, for example, a CD22 CAR comprising the CD22-specific scFv having sequences set forth in SEQ ID NO: 14047 or SEQ ID NO: 14056, the IgG4 hinge domain of SEQ ID NO: 14008 or SEQ ID NO: 14009, the CD28 transmembrane domain of SEQ ID NO: 14012, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD34 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof.

BCMA CAR

In some embodiments, the CAR is a BCMA CAR (“BCMA-CAR”), and in these embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a BCMA CAR. BCMA is a tumor necrosis family receptor (TNFR) member expressed on cells of the B cell lineage, with the highest expression on terminally differentiated B cells or mature B lymphocytes. BCMA is involved in mediating the survival of plasma cells for maintaining long-term humoral immunity. The expression of BCMA has been recently linked to a number of cancers, such as multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma, various leukemias, and glioblastoma. In some embodiments, the BCMA CAR comprises a signal peptide, an extracellular binding domain that specifically binds BCMA, a hinge domain, a transmembrane domain, an intracellular costimulatory domain, and/or an intracellular signaling domain in tandem.

In some embodiments, the signal peptide of the BCMA CAR comprises a CD4 signal peptide. In some embodiments, the CD4 signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14003 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14003. In some embodiments, the signal peptide comprises an IgK signal peptide. In some embodiments, the IgK signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14004 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14004. In some embodiments, the signal peptide comprises a GMCSFR-α or CSF2RA signal peptide. In some embodiments, the GMCSFR-α or CSF2RA signal peptide comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14005 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14005.

In some embodiments, the extracellular binding domain of the BCMA CAR is specific to BCMA, for example, human BCMA. The extracellular binding domain of the BCMA CAR can be codon-optimized for expression in a host cell or to have variant sequences to increase functions of the extracellular binding domain.

In some embodiments, the extracellular binding domain comprises an immunogenically active portion of an immunoglobulin molecule, for example, an scFv. In some embodiments, the extracellular binding domain of the BCMA CAR is derived from an antibody specific to BCMA, including, for example, belantamab, erlanatamab, teclistamab, LCAR-B38M, and ciltacabtagene. In any of these embodiments, the extracellular binding domain of the BCMA CAR comprises or consists of the V_H, the V_L, and/or one or more CDRs of any of the antibodies.

In some embodiments, the extracellular binding domain of the BCMA CAR comprises an scFv derived from C11D5.3, a murine monoclonal antibody as described in Carpenter et al., Clin. Cancer Res. 19(8):2048-2060 (2013). See also PCT Application Publication No. WO2010/104949. The C11D5.3-derived scFv may comprise the heavy chain variable region (V_H) and the light chain variable region (V_L) of C11D5.3 connected by the Whitlow linker, the amino acid sequences of which is provided in Table 14 below. In some embodiments, the BCMA-specific extracellular binding domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14065, 14066, or 14067, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14065, 14066, or 14067. In some embodiments, the BCMA-specific extracellular binding domain comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14067-14069 and 14071-14073. In some embodiments, the BCMA-specific extracellular binding domain comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14067-14069. In some embodiments, the BCMA-specific extracellular binding domain comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14071-14073. In any of these embodiments, the BCMA-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the BCMA CAR comprises or consists of the one or more CDRs as described herein.

In some embodiments, the extracellular binding domain of the BCMA CAR comprises an scFv derived from another murine monoclonal antibody, C12A3.2, as described in Carpenter et al., Clin. Cancer Res. 19(8):2048-2060 (2013) and PCT Application Publication No. WO2010/104949, the amino acid sequence of which is also provided in Table 14 below. In some embodiments, the BCMA-specific extracellular binding domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14074, 14075, or 14079, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14074, 14075, or 14079. In some embodiments, the BCMA-specific extracellular binding domain comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14076-14078 and 14080-14082. In some embodiments, the BCMA-specific extracellular binding domain comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14076-14078. In some embodiments, the BCMA-specific extracellular binding domain comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14080-14082. In any of these embodiments, the BCMA-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the BCMA CAR comprises or consists of the one or more CDRs as described herein.

In some embodiments, the extracellular binding domain of the BCMA CAR comprises a murine monoclonal antibody with high specificity to human BCMA, referred to as BB2121 in Friedman et al., Hum. Gene Ther. 29(5):585-601 (2018)). See also, PCT Application Publication No. WO2012163805.

In some embodiments, the extracellular binding domain of the BCMA CAR comprises single variable fragments of two heavy chains (VHH) that bind to two epitopes of BCMA as described in Zhao et al., J. Hematol. Oncol. 11(1):141 (2018), also referred to as LCAR-B38M. See also, PCT Application Publication No. WO2018/028647.

In some embodiments, the extracellular binding domain of the BCMA CAR comprises a fully human heavy-chain variable domain (FHVH) as described in Lam et al., Nat. Commun. 11(1):283 (2020), also referred to as FHVH33. See also, PCT Application Publication No. WO2019/006072. The amino acid sequences of FHVH33 and its CDRs are provided in Table 14 below. In some embodiments, the BCMA-specific extracellular binding domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14083 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14083. In some embodiments, the BCMA-specific extracellular binding domain comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14084-14086. In any of these embodiments, the BCMA-specific extracellular binding domain comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the BCMA CAR comprises or consists of the one or more CDRs as described herein.

In some embodiments, the extracellular binding domain of the BCMA CAR comprises an scFv derived from CT103A (or CAR0085) as described in U.S. Pat. No. 11,026,975 B2, the amino acid sequence of which is provided in Table 14 below. In some embodiments, the BCMA-specific extracellular binding domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14087, 14088, or 14092, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14087, 14088, or 14092. In some embodiments, the BCMA-specific extracellular binding domain comprises one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14089-14091 and 14093-14095. In some embodiments, the BCMA-specific extracellular binding domain comprises a light chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14089-14091. In some embodiments, the BCMA-specific extracellular binding domain comprises a heavy chain with one or more CDRs having amino acid sequences set forth in SEQ ID NOs: 14093-14095. In any of these embodiments, the BCMA-specific scFv comprises one or more CDRs comprising one or more amino acid substitutions, or comprising a sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical), to any of the sequences identified. In some embodiments, the extracellular binding domain of the BCMA CAR comprises or consists of the one or more CDRs as described herein.

Additionally, CARs and binders directed to BCMA have been described in U.S. Application Publication Nos. 2020/0246381 A1 and 2020/0339699 A1.

TABLE 14
Exemplary sequences of anti-BCMA binder and components

SEQ ID NO:	Amino Acid Sequence	Description
14065	DIVLTQSPASLAMSLGKRATIS-	Anti-BCMA C11D5.3
	CRASESVSVIGAHLIHWYQQKPGQ	scFv entire sequence,
	PPKLLIYLASN-	with Whitlow linker
	LETGVPARFSGSGSGTDFT-
	LTIDPVEEDDVAIYSCLQSRIFPRT-
	FGGGTKLEIKGSTSGSGKPGSGEG
	STKGQIQLVQSGPELKKPGETVKIS
	CKASGYTFTDYSINWVKRAPGKGL
	KWMGWIN-
	TETREPAYAYDFRGRFAFSLETSAS
	TAYLQINNLKYEDTATYFCAL-
	DYSYAMDYWGQGTSVTVSS
14066	DIVLTQSPASLAMSLGKRATIS-	Anti-BCMA C11D5.3
	CRASESVSVIGAHLIHWYQQKPGQ	scFv light chain
	PPKLLIYLASN-	variable region
	LETGVPARFSGSGSGTDFT-
	LTIDPVEEDDVAIYSCLQSRIFPRT-
	FGGGTKLEIK
14067	RASESVSVIGAHLIH	Anti-BCMA C11D5.3
		scFv light chain CDR1
14068	LASNLET	Anti-BCMA C11D5.3
		scFv light chain CDR2
14069	LQSRIFPRT	Anti-BCMA C11D5.3
		scFv light chain CDR3
14070	QIQLVQSGPELKKPGETVKISCK-	Anti-BCMA C11D5.3
	ASGYTFTDYSINWVKRAPGKGLK-	scFv heavy chain vari-
	WMGWIN-	able region
	TETREPAYAYDFRGRFAFSLETSAS
	TAYLQINNLKYEDTATYFCAL-
	DYSYAMDYWGQGTSVTVSS
14071	DYSIN	Anti-BCMA C11D5.3
		scFv heavy chain
		CDR1
14072	WINTETREPAYAYDFRG	Anti-BCMA C11D5.3
		scFv heavy chain
		CDR2
14073	DYSYAMDY	Anti-BCMA C11D5.3
		scFv heavy chain
		CDR3
14074	DIVLTQSPPSLAMSLGKRATIS-	Anti-BCMA C12A3.2
	CRASESVTILGSHLI-	scFv entire sequence,
	YWYQQKPGQPPTLLIQ-	with Whitlow linker
	LASNVQTGVPARFSGSGSRTDFTL
	TIDPVEEDDVAVYYCLQSRTIPRT-
	FGGGTKLEIKGSTSGSGKPGSGEG
	STKGQIQLVQSGPELKKPGETVKIS
	CKASGYTFRHYSMNWVKQAPGKG
	LKWMGRINTESGVPIYADD-
	FKGRFAFSVETSASTAYL-
	VINNLKDEDTASYFCSNDYLYSLD-
	FWGQGTALTVSS
14075	DIVLTQSPPSLAMSLGKRATIS-	Anti-BCMA C12A3.2
	CRASESVTILGSHLI-	scFv light chain
	YWYQQKPGQPPTLLIQ-	variable region
	LASNVQTGVPARFSGSGSRTDFTL
	TIDPVEEDDVAVYYCLQSRTIPRT-
	FGGGTKLEIK
14076	RASESVTILGSHLIY	Anti-BCMA C12A3.2
		scFv light chain CDR1
14077	LASNVQT	Anti-BCMA C12A3.2
		scFv light chain CDR2
14078	LQSRTIPRT	Anti-BCMA C12A3.2
		scFv light chain CDR3
14079	QIQLVQSGPELKKPGETVKISCK-	Anti-BCMA C12A3.2
	ASGYTFRHYSMNWVKQAPGKGLK-	scFv heavy chain
	WMGRINTESGVPIYADDFKGRFAF	variable region
	SVETSASTAYL-
	VINNLKDEDTASYFCSNDYLYSLD-
	FWGQGTALTVSS
14080	HYSMN	Anti-BCMA C12A3.2
		scFv heavy chain
		CDR1
14081	RINTESGVPIYADDFKG	Anti-BCMA C12A3.2
		scFv heavy chain
		CDR2
14082	DYLYSLDF	Anti-BCMA C12A3.2
		scFv heavy chain
		CDR3
14083	EVQLLESGGGLVQPGGSLRLS-	Anti-BCMA FHVH33
	CAASGFTFSSYAMSWVR-	entire sequence
	QAPGKGLEWVSSISGSGDYIY-
	YADSVKGRFTISRDISKNTLYLQMN
	SLRAEDTAVYYCAKEGTGANSSLA
	DYRGQGTLVTVSS
14084	GFTFSSYA	Anti-BCMA FHVH33
		CDR1
14085	ISGSGDYI	Anti-BCMA FHVH33
		CDR2
14086	AKEGTGANSSLADY	Anti-BCMA FHVH33
		CDR3
14087	DIQMTQSPSSLSASVG-	Anti-BCMA CT103A
	DRVTITCRASQSIS-	scFv entire sequence,
	SYLNWYQQKPGKAPKLLIYAAS-	with Whitlow linker
	SLQSGVPSRFSGSGSGTDFTLTISS
	LQPEDFA-
	TYYCQQKYDLLTFGGGTKVEIKGST
	SGSGKPGSGEGSTKGQLQLQESG
	PGLVKPSETLSLTCTVSGGSIS-
	SSSYYWGWIRQPPGKGLEWIG-
	SISYSGSTYYNPSLKSRVTISVDTSK
	NQFSLKLSSVTAADTAVYYCARDR
	GDTILDVWGQGTMVTVSS
14088	DIQMTQSPSSLSASVG-	Anti-BCMA CT103A
	DRVTITCRASQSIS-	scFv light chain
	SYLNWYQQKPGKAPKLLIYAAS-	variable region
	SLQSGVPSRFSGSGSGTDFTLTISS
	LQPEDFA-
	TYYCQQKYDLLTFGGGTKVEIK
14089	QSISSY	Anti-BCMA CT103A
		scFv light chain CDR1
	AAS	Anti-BCMA CT103A
		scFv light chain CDR2
14091	QQKYDLLT	Anti-BCMA CT103A
		scFv light chain CDR3
14092	QLQLQESGPGLVKP-	Anti-BCMA CT103A
	SETLSLTCTVSGGSIS-	scFv heavy chain
	SSSYYWGWIRQPPGKGLEWIG-	variable region
	SISYSGSTYYNPSLKSRVTISVDTSK
	NQFSLKLSSVTAADTAVYYCARDR
	GDTILDVWGQGTMVTVSS
14093	GGSISSSSYY	Anti-BCMA CT103A
		scFv heavy chain
		CDR1
14094	ISYSGST	Anti-BCMA CT103A
		scFv heavy chain
		CDR2
14095	ARDRGDTILDV	Anti-BCMA CT103A
		scFv heavy chain
		CDR3

In some embodiments, the hinge domain of the BCMA CAR comprises a CD4 hinge domain, for example, a human CD4 hinge domain. In some embodiments, the CD4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14006 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14006. In some embodiments, the hinge domain comprises a CD28 hinge domain, for example, a human CD28 hinge domain. In some embodiments, the CD28 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14007 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14007. In some embodiments, the hinge domain comprises an IgG4 hinge domain, for example, a human IgG4 hinge domain. In some embodiments, the IgG4 hinge domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14008 or SEQ ID NO: 14009, or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14008 or SEQ ID NO: 14009. In some embodiments, the hinge domain comprises a IgG4 hinge-Ch2-Ch3 domain, for example, a human IgG4 hinge-Ch2-Ch3 domain. In some embodiments, the IgG4 hinge-Ch2-Ch3 domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14010 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14010.

In some embodiments, the transmembrane domain of the BCMA CAR comprises a CD4 transmembrane domain, for example, a human CD4 transmembrane domain. In some embodiments, the CD4 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14011 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14011. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain, for example, a human CD28 transmembrane domain. In some embodiments, the CD28 transmembrane domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14012 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14012.

In some embodiments, the intracellular costimulatory domain of the BCMA CAR comprises a 4-1BB costimulatory domain, for example, a human 4-1BB costimulatory domain. In some embodiments, the 4-1BB costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14015 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14015. In some embodiments, the intracellular costimulatory domain comprises a CD28 costimulatory domain, for example, a human CD28 costimulatory domain. In some embodiments, the CD28 costimulatory domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14016 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14016.

In some embodiments, the intracellular signaling domain of the BCMA CAR comprises a CD3 zeta (2) signaling domain, for example, a human CD3ζ signaling domain. In some embodiments, the CD37 signaling domain comprises or consists of an amino acid sequence set forth in SEQ ID NO: 14017 or an amino acid sequence that is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in SEQ ID NO: 14017.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a BCMA CAR, including, for example, a BCMA CAR comprising any of the BCMA-specific extracellular binding domains as described, the CD4 hinge domain of SEQ ID NO: 14006, the CD4 transmembrane domain of SEQ ID NO: 14011, the 4-1BB costimulatory domain of SEQ ID NO: 14015, the CD34 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof. In any of these embodiments, the BCMA CAR additionally comprises a signal peptide (e.g., a CD4 signal peptide) as described.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a BCMA CAR, including, for example, a BCMA CAR comprising any of the BCMA-specific extracellular binding domains as described, the CD4 hinge domain of SEQ ID NO: 14006, the CD4 transmembrane domain of SEQ ID NO: 14011, the CD28 costimulatory domain of SEQ ID NO: 14016, the CD34 signaling domain of SEQ ID NO: 14017, and/or variants (i.e., having a sequence that is at least 80% identical, for example, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99 identical to the disclosed sequence) thereof. In any of these embodiments, the BCMA CAR additionally comprises a signal peptide as described.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a BCMA CAR as set forth in SEQ ID NO: 14096 or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence set forth in SEQ ID NO: 14096 (see Table 15). The encoded BCMA CAR has a corresponding amino acid sequence set forth in SEQ ID NO: 14097 or is at least 80% identical (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the amino acid sequence set forth in of SEQ ID NO: 14097, with the following components: CD4 signal peptide, CT103A scFv (V_L-Whitlow linker-V_H), CD4 hinge domain, CD4 transmembrane domain, 4-1BB costimulatory domain, and CD3ζ signaling domain.

In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding a commercially available embodiment of BCMA CAR, including, for example, idecabtagene vicleucel (ide-cel, also called bb2121). In some embodiments, the polycistronic vector comprises an expression cassette that contains a nucleotide sequence encoding idecabtagene vicleucel or portions thereof. Idecabtagene vicleucel comprises a BCMA CAR with the following components: the BB2121 binder, CD4 hinge domain, CD4 transmembrane domain, 4-1BB costimulatory domain, and CD37 signaling domain.

TABLE 15
Exemplary sequences of BCMA CARs

SEQ ID NO:	Sequence	Description
14096	atggccttaccagtgaccgccttgctcctgccgctggcctt-	Exemplary BCMA
	gctgctccac-	CAR nucleotide
	gccgccaggccggacatccagatgacccagtctccatc	sequence
	ctccctgtctgcatctgtaggagacagagtcaccatcac-
	ttgccgggcaagtcagagcatt-
	agcagctatttaaattggtatcagcagaaaccagggaaa
	gcccctaagctcctgatctatgctgcatccagttt-
	gcaaagtggggtcccatcaaggttcag-
	tggcagtggatctgggacagatttcactctcaccatcagc
	agtctgcaacctgaagattttgcaacttactactgtcag-
	caaaaatacgacctcctcac-
	ttttggcggagggaccaaggttgagatcaaaggcagca
	ccagcggctccggcaagcctggctctggcgagggcag-
	cacaaagggacagctgcagctgcag-
	gagtcgggcccaggactggtgaagccttcggagaccct
	gtccctcacctgcactgtctctggtggctccatcagcag-
	tagtagttactactggggctg-
	gatccgccagcccccagggaaggggctggagtggattg
	ggagtatctcctatagtgggagcacctacta-
	caacccgtccctcaagagtcgagtcac-
	catatccgtagacacgtccaagaaccagttctccctgaag
	ctgagttctgtgaccgccgcagacacggcggtg-
	tactactgcgccagagatcgtggagacac-
	catactagacgtatggggtcagggtacaatggtcaccgtc
	agctcattcgtgcccgtgttcctgcccgccaaacctac-
	caccacccctgcccctagac-
	ctcccaccccagccccaacaatcgccagccagcctctgt
	ctctgcggcccgaagcctgtagacctgctgccggcg-
	gagccgtgcacaccagaggcctg-
	gacttcgcctgcgacatctacatctgggcccctctggccg
	gcac-
	ctgtggcgtgctgctgctgagcctggtgatcaccctg-
	tactgcaaccaccg-
	gaacaaacggggcagaaagaaactcctgtatatattca
	aacaaccatttatgagaccagtacaaactactcaagag-
	gaagatggctgtagctgccgat-
	ttccagaagaagaagaaggaggatgtgaactgagagtg
	aagttcagcagatccgccgacgcccctgcctaccag-
	cagggacagaaccagctgtacaac-
	gagctgaacctgggcagacgggaagagtacgacgtgct
	ggacaagcggagaggccgggaccccgagatgggcg-
	gaaagcccagacggaagaacccccag-
	gaaggcctgtataacgaactgcagaaagacaagatgg
	ccgaggcctacagcgagatcgg-
	catgaagggcgagcggaggcgcggcaagggccac-
	gatggcctgtaccagggcctgagcaccgccaccaagga
	cacctacgacgccctg-
	cacatgcaggccctgccccccaga
14097	MAL-	Exemplary BCMA
	PVTALLLPLALLLHAARPDIQMTQSPSSLS	CAR amino acid
	ASVGDRVTITCRASQSIS-	sequence
	SYLNWYQQKPGKAPKLLIYAAS-
	SLQSGVPSRFSGSGSGTDFT-
	LTISSLQPEDFATYYCQQKYDLLTFGGGT
	KVEIKGSTSGSGKPGSGEGSTKGQLQLQ
	ESGPGLVKPSETLSLTCTVSGGSIS-
	SSSYYWGWIRQPPGKGLEWIG-
	SISYSGSTYYNPSLKSRVTISVDTSKNQF
	SLKLSSVTAADTAVYYCARDRGDTIL-
	DVWGQGTMVTVSS-
	FVPVFLPAKPTTTPAPRPPTPAP-
	TIASQPLSLRPEACRPAAGGAVHTRGLDF
	ACDIYIWAPLAGTCGVLLLSLVITLYC-
	NHRNKRGRKKLLY-
	IFKQPFMRPVQTTQEEDGCSCRFPEEEE
	GGCELRVKFSRSADAPA-
	YQQGQNQLYNELNLGR-
	REEYDVLDKRRGRDPEMGGKPRR-
	KNPQEGLYNELQKDKMAEAYSEIGMKGE
	RRRGKGHDGLYQGLSTAT-
	KDTYDALHMQALPPR

In some embodiments, the antibody portion of the recombinant receptor, e.g., CAR, further includes a spacer between the transmembrane domain and extracellular antigen binding domain. In some embodiments, the spacer includes at least a portion of an immunoglobulin constant region, such as a hinge region, e.g., an IgG4 hinge region, and/or a CH1/CL and/or Fc region. In some embodiments, the constant region or portion is of a human IgG, such as IgG4 or IgGI. In some aspects, the portion of the constant region serves as a spacer region between the antigen-recognition component, e.g., scFv, and transmembrane domain. The spacer can be of a length that provides for increased responsiveness of the cell following antigen binding, as compared to in the absence of the spacer. Exemplary spacers include, but are not limited to, those described in Hudecek et al. (2013) Clin. Cancer Res., 19:3153, WO2014031687, U.S. Pat. No. 8,822,647 or published app. No. US 2014/0271635. In some embodiments, the constant region or portion is of a human IgG, such as IgG4 or IgGI.

In some embodiments, the antigen receptor comprises an intracellular domain linked directly or indirectly to the extracellular domain. In some embodiments, the chimeric antigen receptor includes a transmembrane domain linking the extracellular domain and the intracellular signaling domain. In some embodiments, the intracellular signaling domain comprises an ITAM. For example, in some aspects, the antigen recognition domain (e.g. extracellular domain) generally is linked to one or more intracellular signaling components, such as signaling components that mimic activation through an antigen receptor complex, such as a TCR complex, in the case of a CAR, and/or signal via another cell surface receptor. In some embodiments, the chimeric receptor comprises a transmembrane domain linked or fused between the extracellular domain (e.g. scFv) and intracellular signaling domain. Thus, in some embodiments, the antigen-binding component (e.g., antibody) is linked to one or more transmembrane and intracellular signaling domains.

In some embodiments, a transmembrane domain that naturally is associated with one of the domains in the receptor, e.g., CAR, is used. In some instances, the transmembrane domain is selected or modified by amino acid substitution to avoid binding of such domains to the transmembrane domains of the same or different surface membrane proteins to minimize interactions with other members of the receptor complex.

The transmembrane domain in some embodiments is derived either from a natural or from a synthetic source. Where the source is natural, the domain in some aspects is derived from any membrane-bound or transmembrane protein. Transmembrane regions include those derived from (i.e. comprise at least the transmembrane region(s) of) the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. Alternatively, the transmembrane domain in some embodiments is synthetic. In some aspects, the synthetic transmembrane domain comprises predominantly hydrophobic residues such as leucine and valine. In some aspects, a triplet of phenylalanine, tryptophan and valine will be found at each end of a synthetic transmembrane domain. In some embodiments, the linkage is by linkers, spacers, and/or transmembrane domain(s). In some aspects, the transmembrane domain contains a transmembrane portion of CD28.

In some embodiments, the extracellular domain and transmembrane domain is linked directly or indirectly. In some embodiments, the extracellular domain and transmembrane are linked by a spacer, such as any described herein. In some embodiments, the receptor contains extracellular portion of the molecule from which the transmembrane domain is derived, such as a CD28 extracellular portion.

Among the intracellular signaling domains are those that mimic or approximate a signal through a natural antigen receptor, a signal through such a receptor in combination with a costimulatory receptor, and/or a signal through a costimulatory receptor alone. In some embodiments, a short oligo- or polypeptide linker, for example, a linker of 2 to 10 amino acids in length, such as one containing glycines and serines, e.g., glycine-serine doublet, is present and forms a linkage between the transmembrane domain and the cytoplasmic signaling domain of the CAR.

T cell activation is in some aspects described as being mediated by two classes of cytoplasmic signaling sequences: those that initiate antigen-dependent primary activation through the TCR (primary cytoplasmic signaling sequences), and those that act in an antigen-independent manner to provide a secondary or co-stimulatory signal (secondary cytoplasmic signaling sequences). In some aspects, the CAR includes one or both of such signaling components.

The receptor, e.g., the CAR, generally includes at least one intracellular signaling component or components. In some aspects, the CAR includes a primary cytoplasmic signaling sequence that regulates primary activation of the TCR complex. Primary cytoplasmic signaling sequences that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs or ITAMs. Examples of ITAM containing primary cytoplasmic signaling sequences include those derived from CD3 zeta chain, FcR gamma, CD3 gamma, CD3 delta and CD3 epsilon. In some embodiments, cytoplasmic signaling molecule(s) in the CAR contain(s) a cytoplasmic signaling domain, portion thereof, or sequence derived from CD3 zeta.

In some embodiments, the receptor includes an intracellular component of a TCR complex, such as a TCR CD3 chain that mediates T-cell activation and cytotoxicity, e.g., CD3 zeta chain. Thus, in some aspects, the antigen-binding portion is linked to one or more cell signaling modules. In some embodiments, cell signaling modules include a CD3 transmembrane domain, CD3 intracellular signaling domains, and/or other CD transmembrane domains. In some embodiments, the intracellular component is or includes a CD3-zeta intracellular signaling domain. In some embodiments, the intracellular component is or includes a signaling domain from a Fc receptor gamma chain. In some embodiments, the receptor, e.g., CAR, includes the intracellular signaling domain and further includes a portion, such as a transmembrane domain and/or hinge portion, of one or more additional molecules such as CD8, CD4, CD25, or CD16. For example, in some aspects, the CAR or other chimeric receptor is a chimeric molecule of CD3-zeta (CD3-z) or Fc receptor gamma and a portion of one of CD8, CD4, CD25 or CD16.

In some embodiments, upon ligation of the CAR or other chimeric receptor, the cytoplasmic domain or intracellular signaling domain of the receptor activates at least one of the normal effector functions or responses of the immune cell, e.g., T cell engineered to express the CAR. For example, in some contexts, the CAR induces a function of a T cell such as cytolytic activity or T-helper activity, such as secretion of cytokines or other factors. In some embodiments, a truncated portion of an intracellular signaling domain of an antigen receptor component or costimulatory molecule is used in place of an intact immunostimulatory chain, for example, if it transduces the effector function signal. In some embodiments, the intracellular signaling domain or domains include the cytoplasmic sequences of the T cell receptor (TCR), and in some aspects also those of co-receptors that in the natural context act in concert with such receptors to initiate signal transduction following antigen receptor engagement.

In the context of a natural TCR, full activation generally requires not only signaling through the TCR, but also a costimulatory signal. Thus, in some embodiments, to promote full activation, a component for generating secondary or co-stimulatory signal is also included in the CAR. In other embodiments, the CAR does not include a component for generating a costimulatory signal. In some aspects, an additional CAR is expressed in the same cell and provides the component for generating the secondary or costimulatory signal.

In some embodiments, the chimeric antigen receptor contains an intracellular domain of a T cell costimulatory molecule. In some embodiments, the CAR includes a signaling domain and/or transmembrane portion of a costimulatory receptor, such as CD28, 4-1BB, 0X40, DAP10, and ICOS. In some aspects, the same CAR includes both the activating and costimulatory components. In some embodiments, the chimeric antigen receptor contains an intracellular domain derived from a T cell costimulatory molecule or a functional variant thereof, such as between the transmembrane domain and intracellular signaling domain. In some aspects, the T cell costimulatory molecule is CD28 or 41BB.

In some embodiments, the activating domain is included within one CAR, whereas the costimulatory component is provided by another CAR recognizing another antigen. In some embodiments, the CARs include activating or stimulatory CARs, costimulatory CARs, both expressed on the same cell (see WO2014/055668). In some aspects, the cells include one or more stimulatory or activating CARs and/or a costimulatory CAR. In some embodiments, the cells further include inhibitory CARs (iCARs, see Fedorov et al., Sci. Transl. Medicine, 5(215) (December 2013), such as a CAR recognizing an antigen other than the one associated with and/or specific for the disease or condition whereby an activating signal delivered through the disease-targeting CAR is diminished or inhibited by binding of the inhibitory CAR to its ligand, e.g., to reduce off-target effects.

In certain embodiments, the intracellular signaling domain comprises a CD28 transmembrane and signaling domain linked to a CD3 (e.g., CD3-zeta) intracellular domain. In some embodiments, the intracellular signaling domain comprises a chimeric CD28 and CD137 (4-1BB, TNFRSF9) co-stimulatory domains, linked to a CD3 zeta intracellular domain.

In some embodiments, the CAR encompasses one or more, e.g., two or more, costimulatory domains and an activation domain, e.g., primary activation domain, in the cytoplasmic portion. Exemplary CARs include intracellular components of CD3-zeta, CD28, and 4-1BB.

In some embodiments the intracellular signaling domain includes intracellular components of a 4-1BB signaling domain and a CD3-zeta signaling domain. In some embodiments, the intracellular signaling domain includes intracellular components of a CD28 signaling domain and a CD3zeta signaling domain.

In some embodiments, the CAR comprises an extracellular antigen binding domain (e.g., antibody or antibody fragment, such as an scFv) that binds to an antigen (e.g. tumor antigen), a spacer (e.g. containing a hinge domain, such as any as described herein), a transmembrane domain (e.g. any as described herein), and an intracellular signaling domain (e.g. any intracellular signaling domain, such as a primary signaling domain or costimulatory signaling domain as described herein). In some embodiments, the intracellular signaling domain is or includes a primary cytoplasmic signaling domain. In some embodiments, the intracellular signaling domain additionally includes an intracellular signaling domain of a costimulatory molecule (e.g., a costimulatory domain). Examples of exemplary components of a CAR are described in Table 16. In provided aspects, the sequences of each component in a CAR can include any combination listed in Table 16.

TABLE 16
		SEQ ID
Component	Sequence	NO:
Extracellular
binding domain
Anti-CD19 scFv	DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDG	14098
(FMC63)	TVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATY
	FCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEV
	KLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKG
	LEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT
	DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS
Anti-CD19 scFv	DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDG	14099
(FMC63)	TVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATY
	FCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKL
	QESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLE
	WLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDD
	TAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS
Anti-BCMA sdAb	QVQLVESGGGLVQPGGSLRLSCAASGFTFTNHAMSWVRQA	14100
(FHVH74)	PGKGLELVSSISGNGRTTYYADSVKGRFTISRDISKNTLDLQM
	NSLRAEDTAVYYCAKDGGETLVDSRGQGTLVTVSS
Anti-BCMA sdAb	QVQLVESGGGLVQPGGSLRLSCAASGFTFSSHAMTWVRQAP	14101
(FHVH32)	GKGLEWVAAISGSGDFTHYADSVKGRFTISRDNSKNTVSLQM
	NNLRAEDTAVYYCAKDEDGGSLLGYRGQGTLVTVSS
Anti-BCMA sdAb	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP	14102
(FHVH33)	GKGLEWVSSISGSGDYIYYADSVKGRFTISRDISKNTLYLQMN
	SLRAEDTAVYYCAKEGTGANSSLADYRGQGTLVTVSS
Anti-BCMA sdAb	EVQLLESGGGLIQPGGSLRLSCAASGFTFSSHAMTWVRQAP	14103
(FHVH93)	GKGLEWVSAISGSGDYTHYADSVKGRFTISRDNSKNTVYLQM
	NSLRAEDSAVYYCAKDEDGGSLLGHRGQGTLVTVSS
Spacer (e.g.
hinge)
IgG4 Hinge	ESKYGPPCPPCP	14104
CD8 Hinge	TTTPAPRPPTPAPTIASQPLSLRPE	14105
CD28	IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP	14106
Transmembrane
CD8	ACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLY	14107
	C
CD28	FWVLVVVGGVLACYSLLVTVAFIIFWV	14108
CD28	FWVLVVVGGVLACYSLLVTVAFIIFWV	14109
Costimulatory domain
CD28	RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS	14110
4-1BB	KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL	14111
Primary Signaling
Domain
	RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGR	14112
	DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
	RGKGHDGLYQGLSTATKDTYDALHMQALPPR
CD3zeta	RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR	14113
	DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR
	RGKGHDGLYQGLSTATKDTYDALHMQALPPR

In some embodiments, the antigen receptor further includes a marker and/or cells expressing the CAR or other antigen receptor further include a surrogate marker, such as a cell surface marker, which is used to confirm transduction or engineering of the cell to express the receptor. In some aspects, the marker includes all or part (e.g., truncated form) of CD34, a NGFR, or epidermal growth factor receptor, such as truncated version of such a cell surface receptor (e.g., tEGFR). In some embodiments, the nucleic acid encoding the marker is operably linked to a polynucleotide encoding a linker sequence, such as a cleavable linker sequence, e.g., T2A. For example, a marker, and optionally a linker sequence, can be any as disclosed in published patent application No. WO2014031687. For example, the marker can be a truncated EGFR (tEGFR) that is, optionally, linked to a linker sequence, such as a T2A cleavable linker sequence.

In some embodiments, the marker is a molecule, e.g., cell surface protein, not naturally found on T cells or not naturally found on the surface of T cells, or a portion thereof. In some embodiments, the molecule is a non-self molecule, e.g., non-self protein, i.e., one that is not recognized as “self” by the immune system of the host into which the cells will be adoptively transferred.

In some embodiments, the marker serves no therapeutic function and/or produces no effect other than to be used as a marker for genetic engineering, e.g., for selecting cells successfully engineered. In other embodiments, the marker is a therapeutic molecule or molecule otherwise exerting some desired effect, such as a ligand for a cell to be encountered in vivo, such as a costimulatory or immune checkpoint molecule to enhance and/or dampen responses of the cells upon adoptive transfer and encounter with ligand.

In some cases, CARs are referred to as first, second, and/or third generation CARs. In some aspects, a first generation CAR is one that solely provides a CD3-chain induced signal upon antigen binding; in some aspects, a second-generation CAR is one that provides such a signal and costimulatory signal, such as one including an intracellular signaling domain from a costimulatory receptor such as CD28 or CD 137; in some aspects, a third generation CAR is one that includes multiple costimulatory domains of different costimulatory receptors.

For example, in some embodiments, the CAR contains an antibody, e.g., an antibody fragment, a transmembrane domain that is or contains a transmembrane portion of CD28 or a functional variant thereof, and an intracellular signaling domain containing a signaling portion of CD28 or functional variant thereof and a signaling portion of CD3 zeta or functional variant thereof. In some embodiments, the CAR contains an antibody, e.g., antibody fragment, a transmembrane domain that is or contains a transmembrane portion of CD28 or a functional variant thereof, and an intracellular signaling domain containing a signaling portion of a 4-IBB or functional variant thereof and a signaling portion of CD3 zeta or functional variant thereof. In some such embodiments, the receptor further includes a spacer containing a portion of an Ig molecule, such as a human Ig molecule, such as an Ig hinge, e.g. an IgG4 hinge, such as a hinge-only spacer.

In some aspects, the spacer contains only a hinge region of an IgG, such as only a hinge of IgG4 or IgG. In other embodiments, the spacer is or contains an Ig hinge, e.g., an IgG4-derived hinge, optionally linked to a CH2 and/or CH3 domains. In some embodiments, the spacer is an Ig hinge, e.g., an IgG4 hinge, linked to CH2 and CH3 domains. In some embodiments, the spacer is an Ig hinge, e.g., an IgG4 hinge, linked to a CH3 domain only. In some embodiments, the spacer is or comprises a glycine-serine rich sequence or other flexible linker such as known flexible linkers.

For example, in some embodiments, the CAR includes an antibody such as an antibody fragment, including scFvs, a spacer, such as a spacer containing a portion of an immunoglobulin molecule, such as a hinge region and/or one or more constant regions of a heavy chain molecule, such as an Ig-hinge containing spacer, a transmembrane domain containing all or a portion of a CD28-derived transmembrane domain, a CD28-derived intracellular signaling domain, and a CD3 zeta signaling domain. In some embodiments, the CAR includes an antibody or fragment, such as scFv, a spacer such as any of the Ig-hinge containing spacers, a CD28-derived transmembrane domain, a 4-IBB-derived intracellular signaling domain, and a CD3 zeta-derived signaling domain.

The recombinant receptors, such as CARs, expressed by the cells administered to the subject generally recognize or specifically bind to a molecule that is expressed in, associated with, and/or specific for the disease or condition or cells thereof being treated. Upon specific binding to the molecule, e.g., antigen, the receptor generally delivers an immunostimulatory signal, such as an ITAM-transduced signal, into the cell, thereby promoting an immune response targeted to the disease or condition. For example, in some embodiments, the cells express a CAR that specifically binds to an antigen expressed by a cell or tissue of the disease or condition or associated with the disease or condition.

b. T Cell Receptors Antigen Receptors (TCRs)

In some embodiments, engineered cells, such as T cells, used in connection with the provided methods, uses, articles of manufacture or compositions are cells that express a T cell receptor (TCR) or antigen-binding portion thereof that recognizes a protein epitope or T cell epitope of a target protein, such as an antigen of a tumor, viral or autoimmune protein.

In some embodiments, a “T cell receptor” or “TCR” is a molecule that contains variable α and β chains (also known as TCRalpha and TCRbeta, respectively) or a variable γ and δ chains (also known as TCRgamma and TCRdelta, respectively), or antigen-binding portions thereof, and which is capable of specifically binding to a polypeptide bound to an MHC molecule. In some embodiments, the TCR is in the αβ form. Typically, TCRs that exist in αβ and γδ forms are generally structurally similar, but T cells expressing them may have distinct anatomical locations or functions. A TCR can be found on the surface of a cell or in soluble form. Generally, a TCR is found on the surface of T cells (or T lymphocytes) where it is generally responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules.

Unless otherwise stated, the term “TCR” should be understood to encompass full TCRs as well as antigen-binding portions or antigen-binding fragments thereof. In some embodiments, the TCR is an intact or full-length TCR, including TCRs in the ab form or gd form. In some embodiments, the TCR is an antigen-binding portion that is less than a full-length TCR but that binds to a specific peptide bound in an MHC molecule, such as binds to an MHC-peptide complex. In some cases, an antigen-binding portion or fragment of a TCR can contain only a portion of the structural domains of a full-length or intact TCR, but yet is able to bind the peptide epitope, such as MHC-peptide complex, to which the full TCR binds. In some cases, an antigen-binding portion contains the variable domains of a TCR, such as variable a chain and variable b chain of a TCR, sufficient to form a binding site for binding to a specific MHC-peptide complex. Generally, the variable chains of a TCR contain complementarity determining regions involved in recognition of the peptide, MHC and/or MHC-peptide complex.

c. Multi-Targeting

In some embodiments, the cells used in connection with the provided methods, uses, articles of manufacture and compositions include cells employing multi-targeting strategies, such as expression of two or more genetically engineered receptors on the cell, each recognizing the same of a different antigen and typically each including a different intracellular signaling component. Such multi-targeting strategies are described, for example, in WO 2014055668 (describing combinations of activating and costimulatory CARs, e.g., targeting two different antigens present individually on off-target, e.g., normal cells, but present together only on cells of the disease or condition to be treated) and Fedorov et al., Sci. Transl. Medicine, 5(215) (2013) (describing cells expressing an activating and an inhibitory CAR, such as those in which the activating CAR binds to one antigen expressed on both normal or non-diseased cells and cells of the disease or condition to be treated, and the inhibitory CAR binds to another antigen expressed only on the normal cells or cells which it is not desired to treat).

For example, in some embodiments, the cells include a receptor expressing a first genetically engineered antigen receptor (e.g., CAR) which is capable of inducing an activating or stimulatory signal to the cell, generally upon specific binding to the antigen recognized by the first receptor, e.g., the first antigen. In some embodiments, the cell further includes a second genetically engineered antigen receptor (e.g., CAR), e.g., a chimeric costimulatory receptor, which is capable of inducing a costimulatory signal to the immune cell, generally upon specific binding to a second antigen recognized by the second receptor. In some embodiments, the first antigen and second antigen are the same. In some embodiments, the first antigen and second antigen are different.

In some embodiments, the first and/or second genetically engineered antigen receptor (e.g. CAR) is capable of inducing an activating signal to the cell. In some embodiments, the receptor includes an intracellular signaling component containing ITAM or ITAM-like motifs. In some embodiments, the activation induced by the first receptor involves a signal transduction or change in protein expression in the cell resulting in initiation of an immune response, such as ITAM phosphorylation and/or initiation of ITAM-mediated signal transduction cascade, formation of an immunological synapse and/or clustering of molecules near the bound receptor (e.g. CD4 or CD8, etc.), activation of one or more transcription factors, such as NF-KB and/or AP-1, and/or induction of gene expression of factors such as cytokines, proliferation, and/or survival.

In some embodiments, the first and/or second receptor includes intracellular signaling domains or regions of costimulatory receptors such as CD28, CD137 (4-1BB), OX40, and/or ICOS. In some embodiments, the first and second receptor include an intracellular signaling domain of a costimulatory receptor that are different. In some embodiments, the first receptor contains a CD28 costimulatory signaling region and the second receptor contain a 4-IBB co-stimulatory signaling region or vice versa.

In some embodiments, the first and/or second receptor includes both an intracellular signaling domain containing ITAM or ITAM-like motifs and an intracellular signaling domain of a costimulatory receptor.

In some embodiments, the first receptor contains an intracellular signaling domain containing ITAM or ITAM-like motifs and the second receptor contains an intracellular signaling domain of a costimulatory receptor. The costimulatory signal in combination with the activating signal induced in the same cell is one that results in an immune response, such as a robust and sustained immune response, such as increased gene expression, secretion of cytokines and other factors, and T cell mediated effector functions such as cell killing.

In some embodiments, neither ligation of the first receptor alone nor ligation of the second receptor alone induces a robust immune response. In some aspects, if only one receptor is ligated, the cell becomes tolerized or unresponsive to antigen, or inhibited, and/or is not induced to proliferate or secrete factors or carry out effector functions. In some such embodiments, however, when the plurality of receptors are ligated, such as upon encounter of a cell expressing the first and second antigens, a desired response is achieved, such as full immune activation or stimulation, e.g., as indicated by secretion of one or more cytokine, proliferation, persistence, and/or carrying out an immune effector function such as cytotoxic killing of a target cell.

In some embodiments, the two receptors induce, respectively, an activating and an inhibitory signal to the cell, such that binding by one of the receptors to its antigen activates the cell or induces a response, but binding by the second inhibitory receptor to its antigen induces a signal that suppresses or dampens that response. Examples are combinations of activating CARs and inhibitory CARs or iCARs. Such a strategy may be used, for example, in which the activating CAR binds an antigen expressed in a disease or condition but which is also expressed on normal cells, and the inhibitory receptor binds to a separate antigen which is expressed on the normal cells but not cells of the disease or condition.

In some embodiments, the multi-targeting strategy is employed in a case where an antigen associated with a particular disease or condition is expressed on a non-diseased cell and/or is expressed on the engineered cell itself, either transiently (e.g., upon stimulation in association with genetic engineering) or permanently. In such cases, by requiring ligation of two separate and individually specific antigen receptors, specificity, selectivity, and/or efficacy may be improved.

In some embodiments, the plurality of antigens, e.g., the first and second antigens, are expressed on the cell, tissue, or disease or condition being targeted, such as on the cancer cell. In some aspects, the cell, tissue, disease or condition is multiple myeloma or a multiple myeloma cell. In some embodiments, one or more of the plurality of antigens generally also is expressed on a cell which it is not desired to target with the cell therapy, such as a normal or non-diseased cell or tissue, and/or the engineered cells themselves. In such embodiments, by requiring ligation of multiple receptors to achieve a response of the cell, specificity and/or efficacy is achieved.

d. Chimeric Auto-Antibody Receptor (CAAR)

In some embodiments, the recombinant receptor is a chimeric autoantibody receptor (CAAR). In some embodiments, the CAAR binds, e.g., specifically binds, or recognizes, an autoantibody. In some embodiments, a cell expressing the CAAR, such as a T cell engineered to express a CAAR, is used to bind to and kill autoantibody-expressing cells, but not normal antibody expressing cells. In some embodiments, CAAR-expressing cells are used to treat an autoimmune disease associated with expression of self-antigens, such as autoimmune diseases. In some embodiments, CAAR-expressing cells target B cells that ultimately produce the autoantibodies and display the autoantibodies on their cell surfaces, marking these B cells as disease-specific targets for therapeutic intervention. In some embodiments, CAAR-expressing cells are used to efficiently target and kill the pathogenic B cells in autoimmune diseases by targeting the disease-causing B cells using an antigen-specific chimeric autoantibody receptor. In some embodiments, the recombinant receptor is a CAAR, such as any described in U.S. Patent Application Pub. No. US 2017/0051035.

In some embodiments, the CAAR comprises an autoantibody binding domain, a transmembrane domain, and one or more intracellular signaling region or domain (also interchangeably called a cytoplasmic signaling domain or region). In some embodiments, the intracellular signaling region comprises an intracellular signaling domain. In some embodiments, the intracellular signaling domain is or comprises a primary signaling domain, a signaling domain that is capable of stimulating and/or inducing a primary activation signal in a T cell, a signaling domain of a T cell receptor (TCR) component (e.g. an intracellular signaling domain or region of a CD3-zeta) chain or a functional variant or signaling portion thereof), and/or a signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM).

In some embodiments, the autoantibody binding domain comprises an autoantigen or a fragment thereof. The choice of autoantigen can depend upon the type of autoantibody being targeted. For example, the autoantigen may be chosen because it recognizes an autoantibody on a target cell, such as a B cell, associated with a particular disease state, e.g. an autoimmune disease, such as an autoantibody-mediated autoimmune disease. In some embodiments, the autoimmune disease includes pemphigus vulgaris (PV). Exemplary autoantigens include desmoglein 1 (Dsgl) and Dsg3.

In some embodiments, the encoded nucleic acid is operatively linked to a “positive target cell-specific regulatory element” (or positive TCSRE). In some embodiments, the positive TCSRE is a functional nucleic acid sequence. In some embodiments, the positive TCSRE comprises a promoter or enhancer. In some embodiments, the TCSRE is a nucleic acid sequence that increases the level of an exogenous agent in a target cell. In some embodiments, the positive target cell-specific regulatory element comprises a T cell-specific promoter, a T cell-specific enhancer, a T cell-specific splice site, a T cell-specific site extending half-life of an RNA or protein, a T cell-specific mRNA nuclear export promoting site, a T cell-specific translational enhancing site, or a T cell-specific post-translational modification site. In some embodiments, the T cell-specific promoter is a promoter described in Immgen consortium, herein incorporated by reference in its entirety, e.g., the T cell-specific promoter is an IL2RA (CD25), LRRC32, FOXP3, or IKZF2 promoter. In some embodiments, the T cell-specific promoter or enhancer is a promoter or enhancer described in Schmidl et al., Blood. 2014 Apr. 24; 123(17):e68-78., herein incorporated by reference in its entirety. In some embodiments, the T cell-specific promoter is a transcriptionally active fragment of any of the foregoing. In some embodiments, the T-cell specific promoter is a variant having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any of the foregoing.

In some embodiments, the encoded nucleic acid is operatively linked to a “negative target cell-specific regulatory element” (or negative TCSRE). In some embodiments, the negative TCSRE is a functional nucleic acid sequence. In some embodiments, the negative TCSRE is a miRNA recognition site that causes degradation of inhibition of the viral vector in a non-target cell. In some embodiments, the exogenous agent is operatively linked to a “non-target cell-specific regulatory element” (or NTCSRE). In some embodiments, the NTCSRE comprises a nucleic acid sequence that decreases the level of an exogenous agent in a non-target cell compared to in a target cell. In some embodiments, the NTCSRE comprises a non-target cell-specific miRNA recognition sequence, non-target cell-specific protease recognition site, non-target cell-specific ubiquitin ligase site, non-target cell-specific transcriptional repression site, or non-target cell-specific epigenetic repression site. In some embodiments, the NTCSRE comprises a tissue-specific miRNA recognition sequence, tissue-specific protease recognition site, tissue-specific ubiquitin ligase site, tissue-specific transcriptional repression site, or tissue-specific epigenetic repression site. In some embodiments, the NTCSRE comprises a non-target cell-specific miRNA recognition sequence, non-target cell-specific protease recognition site, non-target cell-specific ubiquitin ligase site, non-target cell-specific transcriptional repression site, or non-target cell-specific epigenetic repression site.

In some embodiments, the NTCSRE comprises a non-target cell-specific miRNA recognition sequence and the miRNA recognition sequence is able to be bound by one or more of miR3 1, miR363, or miR29c. In some embodiments, the NTCSRE is situated or encoded within a transcribed region encoding the exogenous agent, optionally wherein an RNA produced by the transcribed region comprises the miRNA recognition sequence within a UTR or coding region.

In some embodiments, the viral vector comprising an anti-CD4 scFv or sdAb composition described herein are administered to a subject, e.g., a mammal, e.g., a human. In such embodiments, the subject is at risk of, has a symptom of, or is diagnosed with or identified as having, a particular disease or condition (e.g., a disease or condition described herein).

In some aspects, resting or non-activated T cells are contacted with a viral vector of the disclosure (e.g., a retroviral vector or lentiviral vector) that includes a CD4 binding agent. The contacting may be performed in vitro (e.g., with T cells derived from a healthy donor or a donor in need of cellular therapy) or in vivo by administration of the viral vector to a subject. In some embodiments the process comprises a) obtaining whole blood from the subject; b) collecting the fraction of blood containing leukocyte components including CD4+ T cells; c) contacting the leukocyte components including CD4+ T cells with a composition comprising the lentiviral vector to create a transfection mixture; and d) reinfusing the contacted leukocyte components including CD4+ T cells and/or the transfection mixture to the subject, thereby administering the lipid particle and/or payload gene to the subject. In some embodiments, the T cells (e.g. CD4+ T cells) are not activated during the method. In some embodiments, step (c) of the method is carried out for no more than 24 hours, e.g., no more than 20, 16, 12, 8, 6, 5, 4, 3, 2, or 1 hour.

In some embodiments, the method according to the present disclosure is capable of delivering a lentiviral particle to an ex vivo system. The method includes the use of a combination of various apheresis machine hardware components, a software control module, and a sensor module to measure citrate or other solute levels in-line to ensure the maximum accuracy and safety of treatment prescriptions, and the use of replacement fluids designed to fully exploit the design of the system according to the present methods. It is understood that components described for one system according to the present invention can be implemented within other systems according to the present invention as well.

In some embodiments, the method for administration of the lentiviral vector to the subject comprises the use of a blood processing set for obtaining whole blood from the subject, a separation chamber for collecting the fraction of blood containing leukocyte components including CD4+ T cells, a contacting container for contacting the CD4+ T cells with the composition comprising the lentiviral vector, and a further fluid circuit for reinfusion of CD4+ T cells to the patient. In some embodiments, the method further comprises any of i) a washing component for concentrating T cells, and ii) a sensor and/or module for monitoring cell density and/or concentration. In some embodiments, the methods allow processing of blood directly from the patient, transduction with the lentiviral vector, and reinfusion directly to the patient without any steps of selection for T cells or for CD4+ T cells. Further the methods also can be carried out without cryopreserving or freezing any cells before or between any one or more of the steps, such that there is no step of formulating cells with a cryoprotectant, e.g. DMSO. In some embodiments, the provided methods do not include a lymphodepletion regimen. In some embodiments, the method including steps (a)-(d) are carried out for a time of no more than 24 hours, such as between 2 hours and 12 hours, for example 3 hours to 6 hours.

In some embodiments, the method for administration of the lentiviral vector to the subject comprises the use of a blood processing set for obtaining whole blood from the subject, a separation chamber for collecting the fraction of blood containing leukocyte components including CD4+ T cells, a contacting container for contacting the CD4+ T cells with the composition comprising the lentiviral vector, and a further fluid circuit for reinfusion of CD4+ T cells to the patient. In some embodiments, the method further comprises any of i) a washing component for concentrating T cells, and ii) a sensor and/or module for monitoring cell density and/or concentration. In some embodiments, the methods allow processing of blood directly from the patient, transduction with the lentiviral vector, and reinfusion directly to the patient without any steps of selection for T cells or for CD4+ T cells. Further the methods also can be carried out without cryopreserving or freezing any cells before or between any one or more of the steps, such that there is no step of formulating cells with a cryoprotectant, e.g. DMSO. In some embodiments, the provided methods do not include a lymphodepletion regimen. In some embodiments, the method including steps (a)-(d) are carried out for a time of no more than 24 hours, such as between 2 hours and 12 hours, for example 3 hours to 6 hours.

Also provided herein are systems for administration of a lentiviral vector comprising a CD4 binding agent to a subject. An exemplary system for administration is shown in FIG. 1.

In some embodiments, the resting or non-activated T cells are not treated with one or more T cell stimulatory molecules (e.g., an anti-CD-3 antibody), one or more T cell costimulatory molecules, and/or one or more T cell activating cytokines. In some embodiments, the resting or non-activated T cells are not treated with any of one or more T cell stimulatory molecules (e.g., an anti-CD-3 antibody), one or more T cell costimulatory molecules, and/or one or more T cell activating cytokines.

In additional aspects, the application includes methods of administration to a subject of a viral vector that includes an anti-CD4 binding agent, wherein the subject is not administered or has not been administered a T cell activating treatment. In some embodiments, the T cell activating treatment includes one or more T cell stimulatory molecules (e.g., an anti-CD-3 antibody), one or more T cell costimulatory molecules, and/or one or more T cell activating cytokines. In some embodiments, the subject is not administered or has not been administered any of one or more T cell stimulatory molecules (e.g., an anti-CD-3 antibody), one or more T cell costimulatory molecules, and/or one or more T cell activating cytokines. In some embodiments, the T cell activating treatment is lymphodepletion. In certain embodiments, the subject is not administered or has not been administered the T cell activating treatment within 1 month before or after administration of the viral vector. In some embodiments, the subject is not administered or has not been administered the T cell activating treatment within 1 month before administration of the viral vector, such as within or at or about 4 weeks, 3 weeks, 2 weeks or 1 weeks, such as at or about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days before administration of the viral vector. In some embodiments, the subject is not administered the T cell activating treatment within 1 month after administration of the viral vector, such as within or at or about 4 weeks, 3 weeks, 2 weeks or 1 weeks, such as at or about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days after administration of the viral vector.

In some aspects, the viral vectors of the disclosure do not include one or more T cell stimulatory molecules (e.g., an anti-CD-3 antibody), one or more T cell costimulatory molecules, and/or one or more T cell activating cytokines.

The use of anti-CD3 antibodies is well-known for activation of T cells. The anti-CD3 antibodies can be of any species, e.g., mouse, rabbit, human, humanized, or camelid. Exemplary antibodies include OKT3, CRIS-7, I2C the anti-CD3 antibody included in DYNABEADS Human T-Activator CD3/CD28 (Thermo Fisher), and the anti-CD3 domains of approved and clinically studied molecules such as blinatumomab, catumaxomab, fotetuzumab, teclistamab, ertumaxomab, epcoritamab, talquetamab, odronextamab, cibistamab, obrindatamab, tidutamab, duvortuxizumab, solitomab, eluvixtamab, pavurutamab, tepoditamab, vibecotamab, plamotamab, glofitamab, etevritamab, and tarlatamab.

In some embodiments, the one or more T cell costimulatory molecules include CD28 ligands (e.g., CD80 and CD86); antibodies that bind to CD28 such as CD28.2, the anti-CD28 antibody included in DYNABEADS Human T-Activator CD3/CD28 (Thermo Fisher) and anti-CD28 domains disclosed in US2020/0199234, US2020/0223925, US2020/0181260, US2020/0239576, US2020/0199233, US2019/0389951, US2020/0299388, US2020/0399369, and US2020/0140552; CD137 ligand (CD137L); anti-CD137 antibodies such as urelumab and utomilumab; ICOS ligand (ICOS-L); and anti-ICOS antibodies such as feladilimab, vopratelimab, and the anti-ICOS domain of izuralimab.

In some embodiments, the one or more T cell activating cytokines include IL-2, IL-7, IL-15, IL-21, interferons (e.g., interferon-gamma), and functional variants and modified versions thereof.

Lymhpodepletion may be induced by various treatments that destroy lymphocytes and T cells in the subject. For example, the lymphodepletion may include myeloablative chemotherapies, such as fludarabine, cyclophosphamide, bendamustine, and combinations thereof. Lymphodepletion may also be induced by irradiation (e.g., full-body irradiation) of the subject.

In some embodiments, the source of targeted lipid particles is the same subject that is administered a targeted lipid particle composition. In other embodiments, they are different. In some embodiments, the source of targeted lipid particles and recipient tissue is autologous (from the same subject) or heterologous (from different subjects). In some embodiments, the donor tissue for targeted lipid particle compositions described herein is a different tissue type than the recipient tissue. In some embodiments, the donor tissue is muscular tissue and the recipient tissue is connective tissue (e.g., adipose tissue). In other embodiments, the donor tissue and recipient tissue are of the same or different type, but from different organ systems.

In some embodiments, the targeted lipid particles (e.g, viral vector) composition described herein are administered to a subject having a cancer, an autoimmune disease, an infectious disease, a metabolic disease, a neurodegenerative disease, or a genetic disease (e.g., enzyme deficiency). In some embodiments, the subject is in need of regeneration.

In some embodiments, the cancer is a T cell-mediated cancer. In another embodiment, the antigen binding moiety portion of a CAR is designed to treat a particular cancer. In some embodiments, the targeted lipid particle is used to treat cancers and disorders including but not limited to non-Hodgkin lymphoma (NHL), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), multiple myeloma, and the like. In some embodiments, the targeted lipid particle is used to treat B cell malignancies, e.g., refractory B cell malignancies.

In some embodiments, the targeted lipid particle is co-administered with an inhibitor of a protein that inhibits membrane fusion. For example, Suppressyn is a human protein that inhibits cell-cell fusion (Sugimoto et al., “A novel human endogenous retroviral protein inhibits cell-cell fusion” Scientific Reports 3:1462 DOI: 10.1038/srep01462). In some embodiments, the targeted lipid particle is co-administered with an inhibitor of sypressyn, e.g., a siRNA or inhibitory antibody.

EXAMPLES

The present disclosure may be further described by the following non-limiting examples, in which standard techniques known to the skilled artisan and techniques analogous to those described in these examples may be used where appropriate. It is understood that the skilled artisan will envision additional embodiments consistent with the disclosure provided herein.

Example 1 Characterization of CD4 Binders

Binders were selected that demonstrated detectable CD4 binding in solution. To assay the ability of the binders to direct cell-specific transduction, the binders were used to generate binder (e.g., as scFv)-Nipah G glycoprotein fusions as described in WO2017182585 for pseudotyping of lentiviral vectors. The Nipah G-linker-binder construct was codon optimized for expression in human cells and sub-cloned into an expression vector for lentivirus generation.

Crude lentiviral production was performed as follows: HEK-293LX cells were plated 24 hours in advance of transfection. On the day of transfection, HEK-293LX cells were transfected with a lentiviral packaging plasmid, the lentiviral transfer plasmid encoding GFP (pSFFV-GFP), and the plasmids encoding for Nipah G protein retargeted for CD4 receptor targeting (NIV-G (CD4)) and Nipah F fusion protein (NiV-Fd22). To harvest the lentivirus, supernatant was removed from the HEK293LX cells and spun at 1000×g for 5 minutes. The supernatant was removed and immediately added to CD4-positive target cells or T cells, or frozen at −80° C. for later use. Lentiviral vectors were produced in both adherent cells and in suspension. In certain experiments, the vectors were filtered using a 0.45 μm filter and concentrated by ultracentrifugation.

To estimate activity of the CD4-retargeted vectors, the supernatants were diluted 1:5 and used to transduce SupT1 cells. After 5 days, the transduced cells were assayed for GFP expression by flow cytometry. The percentage of live cells expressing GFP is shown in Table 17, column “Single point SupT1”. Titer of certain CD4-retargeted vectors was determined by multi-point dilution of vector for transduction of SupT1 cells (adherent and suspension production) (Table 17, columns “Multiple point SupT1 Adh.” and “Multiple point SupT1 Susp.”). Titer was similarly determined using HEK-293T cells overexpressing Macaca nemestrina CD4 to estimate cross-reactivity of the vectors (Table 17, column “Multiple point 293oeNemestrinaCD4”).

TABLE 17
			Multiple point	Multiple point
	Single point	Multiple point SupT1	SupT1 Susp.	293oeNemestri-
	SupT1 1:5 dilution	Adh. titer	titer	naCD4 Adh. titer
Binder	GFP (% GFP)	[Log(TU/mL)]	[Log(TU/mL)]	[Log(TU/mL)]

265	24.1 ± 10.8	5.8 ± 0.25
266	13.1 ± 1.6	5.51 ± 0.05
267	10.1 ± 5.8	5.27 ± 0.25	4.7
263	4.5 ± 7
268	34.7 ± 7.8	6.1 ± 0.09	5.65 ± 0.57
270	56.5 ± 12.1	6.53 ± 0.3	5.32 ± 0.23
271	52.9 ± 11.8	6.51 ± 0.21	5.38 ± 0.28
273	44 ± 12.2	6.29 ± 0.26	5.7 ± 0.51	5.31 ± 0.76
274	23 ± 18	5.8 ± 0.36	5.61 ± 0.13
275	53.9 ± 3.2	6.46 ± 0.24	5.45 ± 0.14
276	9.4 ± 0.1	5.35 ± 0.05
277	4.2 ± 1.5	5.10
278	36.6 ± 5	6.12 ± 0.04	5.3
279	37.5 ± 34.8	6.13 ± 0.67	5.71 ± 0.19
264	11.3 ± 0
257	47.3 ± 1.1	6.1 ± 0.15
280	25.9 ± 2.1	6 ± 0.04	5.34 ± 0.12
282	12.8 ± 1.1	5.51 ± 0.05	5.19 ± 0.12
283	41.1 ± 8.2	6.26 ± 0.11	5.24 ± 0.09
284	17.9 ± 2.3	5.65 ± 0.07
285	5.9 ± 1.8	5.24
286	59.3 ± 25.7	6.23 ± 0.39	5.46 ± 0.03	6.81 ± 0.06
258	49.6 ± 0.8	6.1 ± 0.17
287	38.8 ± 22.8	5.96 ± 0.49	5.28 ± 0.2
288	5.3 ± 0.5	5.18
289	9.8 ± 2.8	5.39 ± 0.12
290	27.7 ± 14.5	5.91 ± 0.4	5.36 ± 0.19
291	0.6 ± 0.5
260	0.2 ± 0
292	21.8 ± 8.3	5.9 ± 0.3	5.63 ± 0.29	6.59 ± 0.03
293	3.9 ± 0.3
294	11.6 ± 2.3	5.45 ± 0.08
295	11.3 ± 8.9	5.74 ± 0.28	5.2 ± 0.19
296	5.8 ± 2.4	5.10
261	3.1 ± 0
297	31.8 ± 4.4	5.89 ± 0.26	5.34 ± 0.14
298	19.9 ± 0.3	5.79 ± 0.12
300	16.3 ± 4.1	5.59 ± 0.12
301	28.2 ± 8.7	5.93 ± 0.21	5.34 ± 0.2
302	0.2 ± 0.2
304	20.7 ± 9.9	5.74 ± 0.28	5.15 ± 0.11
305	30.7 ± 9.9	6.01 ± 0.15	5.26 ± 0.26
306	0.3 ± 0
307	4.7 ± 2	5.24
314	25 ± 4.5	5.89 ± 0.12	5.43 ± 0.21
315	21.3 ± 5.9	5.79 ± 0.14	5.61 ± 0.37
316	0.2 ± 0.1
317	12.5 ± 4.4	5.41 ± 0.15	4.85
319	35.4 ± 17.2	6.16 ± 0.11	5.31 ± 0.18
320	14 ± 7.4	5.44 ± 0.3	5.08 ± 0.21
322	59.7 ± 10.3	6.44 ± 0.2	5.57 ± 0.26
323	20.5 ± 4.5	5.77 ± 0.13
324	14.2 ± 6.9	5.41 ± 0.18	5.02 ± 0.42	4.62
325	21.4 ± 5.1	5.82 ± 0.17	5.44 ± 0.14
326	43.7 ± 7.7	6.25 ± 0.15	5.54 ± 0.25
327	0.3 ± 0
262	0 ± 0
328	23.5 ± 9.1	5.76 ± 0.16	5.49 ± 0.28
329	10.5 ± 2.4	5.34 ± 0.15	4.92 ± 0.11
330	14.1 ± 0.8	5.56 ± 0.02	5.17 ± 0.1
331	24.6± 1.2	5.92 ± 0.04	5.21 ± 0.06
333	22.9 ± 13.6	5.89 ± 0.26	4.85	5.78 ± 1
334	5.5 ± 2.1	5.24		5.25 ± 0.1
335	17.6 ± 2.3	5.64 ± 0.05	5.21 ± 0.12
336	0.1 ± 0.1
337	27.4 ± 6.5	6.01 ± 0.11	5.25 ± 0.07
339	23.1 ± 5.2	5.8 ± 0.13	5.09 ± 0.09
340	13 ± 2.2	5.43 ± 0.15	5.15 ± 0.08
109	17.7 ± 3.5	5.66 ± 0.12	5.17 ± 0.1
110	0.4 ± 0.1
111	57.3 ± 5.4	6.41 ± 0.1	5.62 ± 0.11
112	7.6 ± 1.4	5.28 ± 0.07	5.18	5.37 ± 0.02
1	79.2 ± 6	6.25 ± 0.5	5.84 ± 0.13
113	45 ± 32.1	6.54 ± 0.26	5.68 ± 0.23	4.68 ± 0.08
114	65.2 ± 9.8	6.6 ± 0.11	5.6 ± 0.08
115	27.8 ± 5.9	5.91 ± 0.14	5.44 ± 0.06
23	59.9 ± 7	6.51 ± 0.12	5.69 ± 0.26
116	51.6 ± 9.4	6.4 ± 0.17	5.51 ± 0.05
117	54.1 ± 14	6.45 ± 0.26	5.66 ± 0.25	5.41
2	32.1 ± 3	6.04 ± 0.03	5.61 ± 0.09
118	61.2 ± 2.3	6.57 ± 0	5.6
119	55.4 ± 13.1	6.38 ± 0.23	5.74 ± 0.3	4.73
120	42.3 ± 8.6	6.21 ± 0.06	5.46 ± 0.03
121	0.6 ± 0.6
122	67.1 ± 10.1	6.72 ± 0.07	5.54
123	56.9 ± 2.6	6.57 ± 0	5.65 ± 0.13
38	59.9 ± 14.6	6.51 ± 0.26	5.88 ± 0.31	4.86 ± 0.28
39	53.1 ± 23.1	6.36 ± 0.24	5.67 ± 0.41	5.96 ± 0.76
40	61.8 ± 11.3	6.43 ± 0.21	5.88 ± 0.3	5.39 ± 0.71
41	64.9 ± 7.6	6.52 ± 0.24	5.8 ± 0.4	5.42 ± 0.78
42	61.8 ± 10.1	6.49 ± 0.18	5.95 ± 0.4	5.39 ± 0.69
43	45.2 ± 10.2	6.21 ± 0.1	5.48 ± 0.2	4.68
44	58.3 ± 8.5	6.44 ± 0.2	5.65 ± 0.21	4.81 ± 0.11
45	8.2 ± 1.3	5.25 ± 0.08	5.19 ± 0.27	4.68
46	71.7 ± 11.7	6.56 ± 0.24	5.78 ± 0.18	5.86 ± 0.9
47	77.9 ± 11.1	6.6 ± 0.21	5.77 ± 0.21	5.44 ± 0.92
48	80.7 ± 9.1	6.57 ± 0.47	5.8 ± 0.22	5.53 ± 0.78
49	52.4 ± 13.3	6.36 ± 0.24	5.59 ± 0.27	4.87 ± 0.07
50	77.5 ± 8.8	6.68 ± 0.22	5.76 ± 0.23	5.26 ± 0.96
51	59.4 ± 18.2	6.51 ± 0.3	5.74 ± 0.25	4.6 ± 0.18
52	59 ± 10.7	6.39 ± 0.19	5.57 ± 0.22	5.56 ± 1.02
54	65.3 ± 9.5	6.53 ± 0.24	5.7 ± 0.27	5.2 ± 0.93
55	42.6 ± 2.8	5.94 ± 0.24		5.95 ± 0.2
56	71.8 ± 3.7	6.5 ± 0.15
3	1.2 ± 0.1
4	1 ± 0
6	1.1 ± 0.1
7	1.2 ± 0.4
8	1 ± 0.2
10	0 ± 0
11	1.2 ± 0.2
12	1.3 ± 0.2
13	0.1 ± 0
57	15.5 ± 8.2	5.49 ± 0.21	5.09 ± 0.13	5.17 ± 0.21
125	5 ± 2.3	5.24
129	0.2 ± 0
130	0.2 ± 0.1
131	0.1 ± 0
132	0.1 ± 0.1
134	0.2 ± 0.1
64	0.1 ± 0.1
65	0 ± 0
135	11.4 ± 4.8	5.35 ± 0.2	5.19 ± 0.07	4.56
136	14.3 ± 5.2	5.45 ± 0.2	5.31 ± 0.12	4.62
137	24.7 ± 4.2	5.94 ± 0.06	5.57 ± 0.24	4.56
138	17.4 ± 2.1	5.69 ± 0.1		5.44 ± 0.02
15	38.2 ± 8.6	6.1 ± 0.15	5.4 ± 0.2	5.56 ± 0.83
66	9.1 ± 2.3	5.28 ± 0.12	5.06 ± 0.23
67	23.9 ± 4.8	5.91 ± 0.11	5.22 ± 0.32	4.68
68	25.5 ± 1.2	5.94 ± 0	5.36 ± 0.16	4.68
69	19.7 ± 4.2	5.75 ± 0.17	5.13 ± 0.16	4.52 ± 0.06
24	0.2 ± 0
139	0.1 ± 0.1
140	0 ± 0
141	10.2 ± 5	5.29 ± 0.23	5 ± 0.1	4.56
142	4.6 ± 1.3	5.18		5.29 ± 0.05
70	9.9 ± 2.9	5.38 ± 0.13	5.3 ± 0.08	5.37 ± 0.02
25	0.1 ± 0
144	0.1 ± 0.1
145	0 ± 0
146	56.1 ± 8.2	6.43 ± 0.13	5.76 ± 0.07
147	8.7 ± 0.8	5.33 ± 0.04
148	53.3 ± 14.3	6.35 ± 0.2	5.91 ± 0.23	4.83 ± 0.14
71	62.1 ± 9.5	6.39 ± 0.21	6.04 ± 0.4	5.22 ± 0.54
72	25.5 ± 0.3	5.84 ± 0.06	5.24
73	55.4 ± 23.3	6.41 ± 0.24	6.13 ± 0.28	5.83 ± 0.55
74	58.5 ± 25.4	6.53 ± 0.23	5.99 ± 0.32	5.76 ± 0.55
75	56.3 ± 28.5	6.38 ± 0.38	6.18 ± 0.33	5.49 ± 0.6
149	0.5 ± 0.3			5.13
150	0.1 ± 0.1
26	1.2 ± 0.1			5.24 ± 0.03
77	3.8 ± 2.4	4.96 ± 0.17	4.63 ± 0.04	5.34 ± 0.08
151	0.1 ± 0
152	0.2 ± 0.1
153	0.1 ± 0.1
154	5 ± 0.5	5.10
155	2.7 ± 0.4
156	10.3 ± 1.8	5.41 ± 0.09		4.95 ± 0.1
80	6.1 ± 1.3	5.14 ± 0.09	5.24 ± 0.12
82	15 ± 2	5.57 ± 0.04	5.34 ± 0.14
17	0.1 ± 0.1
157	0.1 ± 0
27	0.1 ± 0
158	0 ± 0
159	10.9 ± 1.7	5.44 ± 0.06
83	20.2 ± 7	5.75 ± 0.19	5.25 ± 0.1	4.62
160	0.1 ± 0
28	1.3 ± 0.4			4.99 ± 0.05
29	0.4 ± 0.1
161	0 ± 0
162	0 ± 0
18	11.7 ± 4.8	5.41 ± 0.17	5.13 ± 0.06
85	23.1 ± 1.7	5.85 ± 0.05	5.05 ± 0.18
164	1 ± 0.1
165	1.3 ± 0.6
87	0 ± 0
32	0.8 ± 0.4
166	17.1 ± 0.5	5.75 ± 0.14
88	36.3 ± 11.5	6.15 ± 0.21	5.37 ± 0.16	5.16 ± 0.19
168	37.6 ± 13.2	5.99 ± 0.28	5.51 ± 0.11	5.42 ± 0.9
89	48.3 ± 16.1	6.19 ± 0.28	5.49 ± 0.22	5.52 ± 1.01
19	0.1 ± 0
91	0 ± 0
92	0 ± 0
93	41.1 ± 12.7	6.12 ± 0.19	5.88	6.36 ± 0.28
176	0.4 ± 0.3
177	0.4 ± 0.1
178	0 ± 0
33	0.1 ± 0.1
179	0.1 ± 0.1
34	0.1 ± 0.1
180	14.6 ± 4	5.55 ± 0.11
95	39.2 ± 20.5	6 ± 0.22	4.77 ± 0.1	5.79 ± 1.02
181	0 ± 0
182	19.4 ± 3.6	5.76 ± 0.14	5.24 ± 0.08	5.02 ± 0.65
97	36.1 ± 14.4	6.06 ± 0.26	5.13 ± 0.09	5.99
99	5.1 ± 0.1	4.91 ± 0.15	4.78
100	6.5 ± 0.8	5.03 ± 0.17	5.03 ± 0.17
36	11.8 ± 3.4	5.47 ± 0.12	5.13 ± 0.1	4.94 ± 0.31
101	35.7 ± 10.9	6.07 ± 0.2	5.31 ± 0.16	5.35 ± 0.64
185	8 ± 2.5	5.22 ± 0.19	5.32 ± 0.13
103	32 ± 8.1	6.04 ± 0.14	5.35 ± 0.17
192	15.4 ± 7.7	5.49 ± 0.26	5.17 ± 0.1	4.88 ± 0.46
193	0.1 ± 0.1
195	14.1 ± 7.2	5.42 ± 0.28	5.17 ± 0.08
104	31.4 ± 10.6	6 ± 0.23	5.24 ± 0.09	5.56 ± 1.2
37	0 ± 0
198	0 ± 0
200	0 ± 0.1
201	0 ± 0
202	0 ± 0
203	66.1 ± 13.8	6.67 ± 0.23	5.7 ± 0.26	5.6 ± 0.98
204	0 ± 0
206	0.4 ± 0.1
208	0 ± 0
210	0 ± 0
211	16.4 ± 8	5.6 ± 0.31		6.61 ± 0.06
213	9 ± 0.2	5.35 ± 0
216	24.1 ± 14.8	5.7 ± 0.45	4.95 ± 0.21	5.66 ± 1.28
217	0 ± 0
218	0.1 ± 0.1
219	0±0
220	0 ± 0
22	0 ± 0
341	0 ± 0
342	0.4 ± 0
343	22 ± 3.1	5.86 ± 0.15
344	11 ± 2.8	5.43 ± 0.11		5.35
345	38.5 ± 4.3	6.06 ± 0.27		6.45 ± 0.04
346	1 ± 0.2
347	0 ± 0
348	21.6 ± 2.4	5.9 ± 0.18
349	0 ± 0
350	41.2 ± 13.6	6.13 ± 0.34	5.1
351	33.3 ± 10	5.89 ± 0.49	5.3 ± 0.08	6.02 ± 0.09
352	3.1 ± 0
353	20.7 ± 0.5	5.84 ± 0.06
354	0.6 ± 0.1
355	18.3 ± 3.1	5.74 ± 0.19
356	2.4 ± 0.4
357	0.9 ± 0.1			5.41
358	39.6 ± 15	6.19 ± 0.17	5.1
359	0.9 ± 0.1
360	0.2 ± 0.1
361	12.7 ± 2	5.49 ± 0.07
362	8.6 ± 1.3	5.35 ± 0.07
363	13.3 ± 3	5.51 ± 0.1
364	60.5 ± 12.3	6.44 ± 0.36	5.8	5.75 ± 0.69
259	54.9 ± 6.8	6.24 ± 0.13		5.97 ± 0.12
365	2.4 ± 0.3
366	20.5 ± 2	5.83 ± 0.14
367	51.8 ± 16.3	6.54 ± 0.19	5.49 ± 0.07
368	7 ± 0.4	5.24 ± 0
369	37.7 ± 18.8	6.13 ± 0.25	5.33 ± 0.04	6.59 ± 0.24
370	11 ± 1	5.44 ± 0.06
371	5.9 ± 0.8	5.14 ± 0.06		5.4 ± 0.07
372	2.5 ± 0.7
373	0.1 ± 0.1
374	24 ± 4.2	6.02 ± 0.11
375	24.6 ± 0.5	6.03 ± 0.04
376	8.8 ± 1.1	5.35 ± 0.07
377	0.7 ± 0.1
378	21 ± 0.2	5.88 ± 0	5.18
379	45.9 ± 12.1	6.23 ± 0.24	5.64 ± 0.02
380	6.7 ± 0.7	5.21 ± 0.05
381	1.4 ± 0.7
382	49 ± 0.2	6.2 ± 0.16	5.1	6.67 ± 0.07
383	11.3 ± 0.9	5.46 ± 0.03
384	51.2 ± 1.1	6.23 ± 0.18	5.24
385	17.6 ± 8.9	5.62 ± 0.26		6.57
386	45.1 ± 13.3	6.25 ± 0.15	5.24 ± 0.09	6.24 ± 0.09
223	2.4 ± 0.4
224				6.45 ± 0.04
106	0.9 ± 0.1			6.45 ± 0.04
225	1.5 ± 0.1
226	0.1 ± 0
228	15.5 ± 1.1	5.39 ± 0.16		6.21 ± 0.1
229	0.6 ± 0.4
107	0.1 ± 0.1
238	0±0
239	0 ± 0
240	0.1 ± 0
241	41.1 ± 2.1	5.77 ± 0.24		5.99 ± 0.11
243	1.7 ± 0.6
256	60.5 ± 11.3	6.31 ± 0.4	6.37 ± 1.18	5.91 ± 1.33

Titer was also determined on SupT1 cells following concentration of the viral vector compositions (Table 26).

TABLE 26
						SupT1 titer
				SupT1 titer	SupT1 titer	(concentrated,
		CD4	Nemestrina	(crude,	(crude,	suspension,
		domain	Cross-	adherent,	suspension,	PE) TU/mL
Binder	Modality	specificity	Reactivity	PE) TU/mL	PE) TU/mL	[conc factor]*
387	DARPin	Domain 1	Cross-	6.50E6 ±	2.33E6*	1.2E8
			reactive	1.47E6		[200X]
256	VHH	Domain 2	Cross-	4.73E6 ±	2.34E6*	5.22E7
(VHH4)*			reactive	2.79E6		[200X]
388*	VHH	Domain 3/4*	Cross-	1.18E ±	Too low*	5.45E6
			reactive	1.26E6		[200]
279	scFv	Domain 3/4	No cross-	2.85E6 ±	5.50E5 ±	1.43E8
			reactivity	3.35E6	2.46E5	[200X]
286	scFv	Domain 3/4	Cross-	2.27E6 ±	2.88E5 ±	5.47E7
			reactive	1.78E6	1.77E4	[200X]
287	scFv	Domain 2	No cross-	1.73E6 ±	1.94E5 ±	3.83E7
			reactivity	1.29E6	8.40E4	[200X]
322	scFv	Domain 3/4	No cross-	3.03E6 ±	4.40E5 ±	4.66E7
			reactivity	1.42E6	3.25E5	[200X]
47	scFv	Domain 1/2	Cross-	4.39E6 ±	6.47E5 ±	6.86E7
			reactive	1.98E6	3.21E5	[200X]
48	scFv	Domain 1/2	Cross-	5.91E6 ±	6.93E5 ±	8.75E7
			reactive	4.47E6	3.22E5	[200X]
75	scFv	Domain 2	Cross-	3.80E6 ±	1.44E6	1.36E8
			reactive	1.75E6		[200X]
364	scFv	Domain 2	Cross-	3.41E6 ±	7.42E5	5.67E7
			reactive	1.70E6		[200X]

Off-target transduction directed by certain binders was determined using CD4 knockout SupT1 cells and HEK-293T cells, which were determined to be negative for CD4 expression. CD4-retargeted vectors expressing GFP were produced in either adherent or suspension culture, as described above, and used to transduce CD4 knockout SupT1 cells and HEK-293T cells at a single dilution. The percentage of GFP-expressing cells was determined by flow cytometry (FIG. 2).

Transduction efficiency on human PBMCs and Pan T cells was also determined for CD4-targeted lentiviral vectors. Concentrated vector was produced as described above and used to transduce human PBMCs from 3 donors, and the transduced cells were assayed for GFP expression by flow cytometry five days after transduction. The flow cytometry results are presented in FIG. 3. The percent of live cells that were GFP+ are shown in FIG. 4 The vectors showed a strong specificity for CD4+ cells vs. CD4− cells.

Binding kinetics of certain CD4 binders were assayed using biolayer interferometry (BLI). The CD4 binders were expressed as homodimers with mouse Fc. Human CD4-Fc was used as the capture reagent. Kinetic parameters are shown in Table 18 below.

TABLE 18
Binder	Conc [nM]	KD [nM]	Kon [1/Ms]	Koff [1/s]

387	250	7	2.47E+04	1.75E−05
256	500	5.14	8.95E+04	4.60E−04
279	125	5	4.17E+04	2.10E−04
286	125	13.8	7.19E+02	2.70E−04
322	62.5	1.7	9.94E+04	1.75E−04
47	62.5	0.3	4.79E+05	5.70E−05
75	62.5	0.7	3.12E+05	2.05E−04
364	62.5	7.54	3.04E+04	2.30E−06

Example 2. Transduction of Resting T Helper Cells Using a CD4 Targeted Fusogen to Generate CAR T Cells

A CD19-specific CAR encoding 4-1BB and the CD3zeta endodomains (CD 19 CAR) was generated to examine CD4+ CAR T transduction efficiency and functionality. PBMCs were thawed and activated with anti-CD3/anti-CD28 beads and exposed to GFP-expressing CD4 fusosomes (Binder 256), and specificity of targeting CD4+ T cells was measured by flow cytometry.

CD19 CAR fusosomes targeting CD4 were used to test transduction efficiency against activated (CD3/CD28 or IL-7 treated) or resting CD4+ T cells, and to measure T cell function against CD19+ and CD19 CRISPR/Cas9-knockout lymphoma cells (Nalm-6) (e.g., tumor co-culture and rechallenge assays and cytokine production) in vitro. Vector copy number (VCN) was determined by a multiplex digital droplet polymerase chain reaction (ddPCR) assay and reported as copies per diploid genome (c/dg). CD4-targeted CD 19 CAR fusosomes could efficiently transduce both activated (34%+1.5% CD4+ CAR+; 0.54±0.18 c/dg), and resting CD4-selected T cells, albeit at a lower expression and integration level (20%±0.5% CD4+ CAR+; 0.28±0.14 c/dg). Resting CD4-transduced CART cells demonstrated specific cytotoxicity and cytokine production (GM-CSF, IFN-γ, TNF-α, IL-2, IL-6, and IL-10) against CD19+ Nalm-6 cells, but did not recognize CD19 knockout tumor cells. In long-term co-culture assays (9-day) with repetitive stimulation with fresh tumor cells (3×), CD4+CD 19 CAR T cells transduced without prior activation continued to show potent tumor cell killing.

CD4-specific fusosomes encoding LVV were observed to efficiently deliver an integrating CAR payload to resting and activated CD4+ T cells. Modified CD4+ CAR T cells demonstrated potent anti-tumor activity against CD19+ tumor cells. These data are consistent with a finding that targeting the CD4 co-receptor through in vivo delivery using a novel pseudotyped LVV can produce functional CAR T cells.

Example 3. CD4-Targeted Fusosomes Reduce CD19+ Tumor Burden In Vivo

CD4-targeted CD19 CAR fusosomes (lentiviral vector) were generated substantially as described above and assessed for their ability to reduce tumor burden in vivo. The fusosomes were pseudotyped with Nipah virus fusogen retargeted with CD4 Binder 256, CD4 Binder 75, and a CD8 Binder Control. NSG mice (n=5/group) were injected with 1E6 Nalm6-Luc leukemia B cells via intravenous (IV) tail injection, followed three days later by an IV tail injection of 1E7 human peripheral blood mononuclear cells (hPBMC). A day after hPBMC injection, 2.5E6, 5E6, or 1E7 integrating units (IU) of CD4-targeted CD19 CAR fusosomes were injected into separate groups of mice via the same route and volume. Beginning 1 day following fusosome injection, Nalm6 tumor progression was tracked via bioluminescent imaging (BLI) weekly throughout the duration of the study. Tumor growth data is represented as total flux (photons/sec). In addition, peripheral blood was collected from all animals on study day 15 to assess the presence of CAR+ T− cells in peripheral blood using flow cytometry. The CD19 CAR contained an anti-scFv directed against CD19 and an intracellular signaling domain containing intracellular components of 4-1BB and CD3-zeta.

As shown in FIGS. 5A and 5B, dose dependent tumor control was observed with Binder 256 and CD8 Control Binder at Day 21. Binder 75 showed a reduced ability to control Nalm6 growth, as shown in FIG. 5C. As shown in FIG. 5D, expression of the CAR in CD4+ T cells was dose-dependent. These data indicate that in vivo delivery of a CD19 CAR transgene payload with CD4-targeted fusosomes in CD19+ tumor bearing mice demonstrates robust production of CAR T cells and CD19+ tumor eradication.

TABLE 19
Full Binder Sequences
Table 19-Full length sequences

	Binder	SEQ ID
Sequence	Name	NO:

QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEIFPGS	1	1
GHTSFNEKFKGKATFTADTSSNTAYIQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINSY
LSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCL
QYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTLSSYWIEWVKQRPGHGLEWIGEILPGS	2	2
GSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGATSYNQKFK	3	3
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGEYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQLLVFAATYLADGVPSRFSGSGSGTQYSLKINSLQSEDFGNYYCQHFWGTPWT
FGGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	4	4
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWT
FGGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTSYNQKFK	5	5
GKATFTVDTSSSTAYMHFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQVLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGSPWT
FGGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	6	6
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPRLLVYAATNLADGVPSRFSGSGSGTQYSLKITSLQSEDFGSYYCQHFWGTPWTF
GGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGANGYNQKFK	7	7
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWT
FGGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	8	8
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQVLVYAATNVADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWT
FGGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	9	9
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASDNIYSNLAWYQQKQGK
SPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWT
FGGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	10	10
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPRLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTF
GGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	11	11
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLAVSSG
GGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQG
KSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPW
TFGGGTKLEIK
LVKTGASVKISCKASGYSFTGFYMHWVKQSHGKGLEWIGYISSYNGATGYNQKFK	112	12
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQLLVFAATYLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTF
GGGTKLEIK
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGATGYNQKFK	13	13
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGK
SPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGSPWT
FGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	14	14
PNSGTTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAY
WGQGTLVTVSAGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSV
SYMHWFQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTFSSMEAEDAAT
YYCQQWSSNPLYTFGGGTKLEIK
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	15	15
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGGGTKLELK
QVQLQQPGAELIKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	16	16
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFVYWG
QGTLVTVSAGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVK
NLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTINNLESEDFADYYC
LQFYEFPLTFGAGTKLELK
EVQLQQSGAELVKPGASVKLSCTPSGFNIKDTSLHWVKQGPEQGLEWIGRIDPAN	17	17
GNTKYDPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCARGPDDGYFYYYSMD
YWGQGTSVTVSSGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASEN
IYSNLAWYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFG
SYYCQHFWGTPWTFGGGTKLEIK
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	18	18
TYTGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDMATYFCARKYYDYEFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIVMTQSPSSLAMSVGQKVTMSCKSSQSL
LNSSNQKNYLAWYQQKPGQSPKLLVYFASTRESGVPDRFIGSGSGTDFTLTISSVQ
AEDLADYFCQQHYSTPLTFGAGTKLELK
QVQLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	19	19
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHEEANWAWFAY
WGQGTLVTVSAGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTITCSASSSVS
YMHWFQQKPGTSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISRMEAEDAATY
YCQQRSSFPYTFGGGTKLEIK
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	20	20
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCASYYGSSRSYWYLDV
WGAGTTVTVSSGGGSGGGGSGGGGSSIVMTQTPKFLLVSAGDRVTITCKASQSV
SNDVAWYQQKPGQSPKLLIYYASNRYTGVPDRFTGSGYGTDFTFTISTVQAEDLA
VYFCQQDYTSLPTFGAGTKLEIK
QVKLVESGGDLVKPGGSLKLSCATSGFTFSSYGMSWVRQTPDKRLEWVATISSGG	21	21
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEGTAMYYCARHNYSNWDWFAY
WGQGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPSSLSASLGDTITITCHASQNI
NVWLSWYQQKPGNIPKLLIYKASNLHTGVPSRFSGSGSGTGFTLTISSLQPEDIATY
YCQQGQSYPLTFGGGTNLEIK
EVQLQQSGAELVKPGASVKLSCTPSGFNIKDTSLHWVKQGPEQGLEWIGRIDPAN	22	22
GNTKYDPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCARGPDDGYFYYYSMD
YWGQGTSVTVSSGGGSGGGGSGGGGSETTVTQSPASLSMAIGEKVTIRCITSTDI
DDDMNWYQQKPGEPPKLLISEGNSLRPGVPSRFSSSGYGTDFVFTIENMLSEDVA
DYYCLQSDNLPLTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	23	23
GSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELK
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGLIDP	24	24
SDSETHYNQVFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDVYYRFAYWG
QGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPSSLSASLGGKVTITCKASQDINKY
IAWYQHKPGKGPSLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIATYYCLQY
DNLMYTFGGGTKLEIK
QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWINWVKQRPGQGLEWIGNIYPS	25	25
DSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRGNYIDYWGQGT
TLTVSSGGGSGGGGSGGGGSENVLTQSPAIMSASLGEKVTMSCRASSSVNYMY
WYQQKSDASPKLWIYYTSNLAPGVPGRFSGSGSGNSYSLTISSMEGEDAATYYCQ
QFTSSHTFGGGTKLEIK
QVQLKESGPGLVAPSQSLSIPCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAG	26	26
GTTNYNSALMSRLSISKDNSKSQVFLKMYSLQTDDTAMYYCARGDGYDDGYAM
DYWGQGTSVTVSSGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASQ
SVSTSSYSYMHWYQQKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLNIHPVE
EEDTATYYCQHSWEIPLTFGAGTKLELK
QVQLQQSGAELVKPGASVKLSCKASGSTFTTYYIYWVKQRPGQGLEWIGEINPSN	27	27
GGTNFNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTSYYTHETYYYAMDY
WGQGTSVTVSSGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVSIRCMTSIDID
DDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENTLSEDVADY
YCLQSDNMPFTFGSGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMQWVKQRPGQGLEWIGEIDP	28	28
SDSYTNYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARAEYGYGNYPW
FAYWGQGTLVTVSAGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSST
GAVTTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQ
TEDDAMYFCALWYSTHWVFGGGTKLTVL
QVQLQQPGAELVKPGASVKVSCKASGYTFTSYWMHWVKQRPGQGLEWIGRIHP	29	29
SDSDTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAIPYYYGGWYFDV
WGTGTTVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSSTGAV
TTSNYANWVQEKPDHLFTGLIGGTNNRAPGVPARFSGSLIGDKAALTITGAQTED
EAIYFCALWYSNHLFGSGTKVTVL
EVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	30	30
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARLYDAHWDYFDYW
GQGTTLTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSSTGAVTT
SNYANWVQEKPDHLFTGLIGGTNNRAPGVPARFSGSLIGDKAALTITGAQTEDEAI
YFCALWYSNHWVFGGGTKLTVL
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	31	31
NSGNTNYNEKFKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCAIYYDYDAYYFDYW
GQGTTLTVSSGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVK
NLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYYC
LQFYEFPYTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	32	32
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCANPYYGYDVGY
WGQGTTLTVSSGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSV
SYMYWYQQKPGSSPRLLIYDTSNLASGVPVRFSGSGSGTSYSLTISRMEAEDAATY
YCQQWSSYPLTFGAGTKLELK
EVQLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	33	33
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRHDDSSYDWFAYW
GQGTLVTVSAGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVTIRCITSTDIDDD
MNWYQQKPGEPPKLLISEGNTLRPGVPSRFFSGGYGTDFVFTIENTLSEDVADYYC
LQSDNMPLMFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWMHWVKQRPGQGLEWIGMIH	34	34
PNSGTTNYNEKFKSKATLTVDKSSSTTYMQLISLTSEDSAVYYCARFGDGYHFDYW
GQGTTLTVSSGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTITCSASSSVSY
MHWFQQRPGTSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISRMEAEDAATYY
CQQRSTYPTFGGGTKLEIK
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	35	35
TNTGEPTYAEEFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARWYPYFDYWGQ
GTTLTVSSGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVKNL
NWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYYCLQ
FYEFPYTFGGGTKLEIK
QVQLQQSGAELAKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGYINP	36	36
SSGYTKYNQKFKDKATLTADKSSSTAYMQLSSLTYEDSAVYYCARSDGSSGNWYF
DVWGTGTTVTVSSGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASG
NIHNYLAWYQQKQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINSLQPED
FGSYYCQHFWSTPWTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	37	37
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAM
DYWGQGTSVTVSSGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASE
NIYSNLAWYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDF
GSYYCQHFWGTPYTFGGGTKLEIK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	38	38
GSTSYNEKFKDKATFTADTSSNTAFMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPLTFGGGTKLEIKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVRQAPGHGLEWIGEVLPG	39	39
SGSTSYNEKFKGRATFTADTSSNTAYMQLSSLRSEDSAVYYCARRAYGYDEGFDY
WGQGTTVTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINGYLSWYQQKPGKSPQTLLYRANRLVDGVPSRFRGSGSGQDYTLTISSLEYED
MGTYYCLQYDEFPPTFGGGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVRQAPGHGLEWIGEILPGS	40	40
GRTSYIEKFKGRATFTADTSSNTAYMQLSSLRSEDSAVYYCARRGYGYDEGFDYW
GQGTTVTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWYQQKPGKSPKTLIYRAKRLVDGVPSRFSGSGSGQDYTLTISSLEYEDMGT
YYCLQYDEFPPTFGGGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEVLPG	41	41
SGSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINGYLSWFQQKPGKSPQTLLYRANRLVDGVPSRFRGSGSGQDYSLTISSLEYEDM
GIYYCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	42	42
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRAKRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	43	43
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLHYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	44	44
DSTSYNEKFKGKTTFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATAYTFSIYWIEWVKQRPGHGLEWIGEILPGS	45	45
GSTNYNEKVKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDM
GIYYCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEIFPGS	46	46
GHTSFNEKFKGKATFTADTSSNTAYIQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKMSCKATGYTFSNYWIEWVKQRPGHGLEWIGEILP	47	47
GSGSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDY
WGQGSTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDM
GIYYCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	48	48
GSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVQQRPGHGLEWIGEILPG	49	49
SGYTSYIEQFKGKATFTADTSSNTAYMQLGSLTSEDSAVYYCARRGYGYDEGFDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINSYLSWFHQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMG
IYYCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTLSSYWIEWVKQRPGHGLEWIGEILPGS	50	50
GSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKGTGYTFSSYWIEWVKQRPGHGLEWIGEISPGS	51	51
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFGTYWIEWVKQRPGHGLEWIGEILPG	52	52
SGTPNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDAGFDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDM
GFYYCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKISFKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	53	53
GSTSCNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSIYASLGERVTITCKASQDINS
YLNWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGVGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	54	54
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELKR
QVQLQQSGAELMKPGASVKMSCKATGYTFSNYWIEWVKQRPGHCLEWIGEILP	55	55
GSGSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDY
WGQGSTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQ
DINSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDM
GIYYCLQYDEFPPTFGCGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHCLEWIGEILPGS	56	56
GSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGCGTKLELKR
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	57	57
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSSGG
GGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASDNIYSNLAWYQQKQG
KSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPW
TFGGGTKLEIKR
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGATSYNQKFK	58	58
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGEYFDYWGQGTTLTVSSGG
GGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQG
KSPQLLVFAATYLADGVPSRFSGSGSGTQYSLKINSLQSEDFGNYYCQHFWGTPW
TFGGGTKLEIKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLSSYGVHWVRQSPGKALEWLGVIWRG	59	59
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGAKLELKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTSYGVHWVRQSPGKGLEWLGVIWRG	60	60
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDSAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASEN
VVTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLA
DYHCGQSYSYPFTFGSGTKLEIKR
QVQLKQSGPGPVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWRG	61	61
GSTDNNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASEN
VVTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLA
DYHCGQSYSYPFTFGSGTKLEIKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTRYGVHWVRQSPGKGLEWLGVIWRG	62	62
GSTDHNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASEN
VVTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLA
DYHCGQSYSYPFTFGSGTKLEIKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTTYGVHWVRQSPGKGLEWLGVIWRG	63	63
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASEN
VVTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLA
DYHCGQSYSYPFTFGSGTKLEIKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	64	64
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAY
WGQGTLVTVSAGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASS
SVSYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDA
ATYYCQQWSSNPLYTFGGGTKLEIKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	65	65
PNSGTTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAY
WGQGTLVTVSAGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASS
SVSYMHWFQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTFSSMEAEDA
ATYYCQQWSSNPLYTFGGGTKLEIKR
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	66	66
SGSTYYNEKFKGKATLTADKSSNTVYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVD
YDGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEE
DAATYYCQQSNEDPLTFGAGTKLELKR
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	67	67
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVD
YDGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEE
DAATYYCQQSNEDPLTFGAGTKLELKR
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	68	68
SGSSYYNEKFRGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVD
YDGDSYMNWYQQKPGQPPQLLIYAASNLQSGIPARFSGSGSGTDFTLNIHPVEEE
DAATYYCQQSNEDPLTFGAGTKLELKR
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQKTGQGLEWIGEIYPG	69	69
SGSSYYNEKFKGKATLTADKSSNTAYIQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFGGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGAGTKLELKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	70	70
PNSGSPNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFAYW
GQGTLVTVSAGGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDI
VKNLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADY
YCLQFYEFPLTFGAGTKLELKR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	71	71
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNKDPLTFGAGTKLELKR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	72	72
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNKDPLTFGAGTKLELKR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	73	73
SGSNYYNEKFKGKAIMTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWG
QGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGAGTKLELKR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	74	74
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNKDPFTFGAGTKLELKR
/QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVRQAPGQGLEWIGEIYP	75	75
GSGSSYYNEKFKGRATLTADKSSNTAYMQLSSLRSEDSAVYFCARPGDLGFAYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIVLTQSPSSLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLTIHPVEEEDA
ATYYCQQSNKDPFTFGGGTKLELKR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	76	76
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNKDPFTFGAGTKLELKR
QVQLKESGPGLVAPSQSLSITCTVSGFSLTNYGVHWVRQPPGKGLEWLGVVWAG	77	77
GITNYNWALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARGDGYDDGYAM
DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRAS
QSVSTSSYSYMHWYQQKPGQAPKLLIKYASNLESGVPARFSGSGSGTDFTLNIHPV
EEEDTATYYCQHSWEIPLTFGAGAKLELKR
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVLWAG	78	78
GITNYNSALMSRLSIRKDNSKSQVFLKMYSLHTDDTAMYYCARGDGYDDGYAMD
YWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASQ
SVSTSSYSYMHWYQQKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLNVHPV
EEEDTATYYCQHSWEIPLTFGAGTKLELKR
QVQLKESGPGLVAPSQSLSIPCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAG	79	79
GTTNYNSALMSRLSISKDNSKSQVFLKMYSLQTDDTAMYYCARGDGYDDGYAM
DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRAS
QSVSTSSYSYMHWYQQKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLNIHPV
EEEDTATYYCQHSWEIPLTFGAGTKLELKR
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	80	80
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGA
VTTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTED
DAMYFCALWYSTHYVFGGGTKVTVLR
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYIHWVKQRPEQGLEWIGWIDPEN	81	81
GDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSSMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAV
TTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTEDD
AMYFCALWYSTHYVFGGGTKVTVLR
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	82	82
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNVALLRYSSAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGA
VTTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTED
DAMYFCALWYSTHYVFGGGTKVTVLR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	83	83
SGSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVD
YDGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEE
DAATYYCQQSNEDPLTFGAGTKLELKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMQWVKQRPGQGLEWIGEIDP	84	84
SDSYTNYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARAEYGYGNYPW
FAYWGQGTLVTVSAGGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSS
TGAVTTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGA
QTEDDAMYFCALWYSTHWVFGGGTKLTVLR
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	85	85
TYTGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDMATYFCARKYYDYEFAYW
GQGTLVTVSAGGGGSGGGGSGGGGSDIVMTQSPSSLAMSVGQKVTMSCKSSQS
LLNSSNQKNYLAWYQQKPGQSPKLLVYFASTRESGVPDRFIGSGSGTDFTLTISSV
QAEDLADYFCQQHYSTPLTFGAGTKLELKR
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	86	86
TGGTAYNQKFKVKAILTADKSSSTAYMELRSLTSEDSAVYYCTRLGDYDVMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISN
YLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFC
QQDNTLPRTFGGGTKLEIKR
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	87	87
NSGNTNYNEKFKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCAIYYDYDAYYFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIV
KNLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYY
CLQFYEFPYTFGGGTKLEIKR
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	88	88
SGSNYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCAREEKIYFDYWGQG
TTLTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDG
DSYMNWYRQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAAT
YYCQQSNEDPWTFGGGTKLEIKR
EVQLQQSGTVLARPGASVKMSCKTSGYTFTSYWMHWIKQRPGQGLEWIGAIYP	89	89
GNSDTTYNQKFKGKAKLTAVTSASTAYMELSSLTNEDSAVYYCTSLITTAYYFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIV
KNLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYY
CLQFYEFPLTFGAGTKLELKR
QVQLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	90	90
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHEEANWAWFAY
WGQGTLVTVSAGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTITCSASSS
VSYMHWFQQKPGTSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISRMEAEDAA
TYYCQQRSSFPYTFGGGTKLEIKR
QVQLQQSGPQLVSPGASVKISCKASGYSFTNYWMHWVKQRPGQGLEWIGMID	91	91
PSDSETRLNQQFKDKATLTVDESSSTAYMQLSSPTSEDSAVYYCAIPYYAMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDIN
SYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYY
CLQYDEFPLTFGAGTKLELKR
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	92	92
NSGNTNYNEKNKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCATYYGNYVWYFD
VWGAGTSVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASLGERVSLTCRASQ
DIHGYLNLFQQKPGETIKHLIYETSNLDSGVPKRFSGSRSGSDYSLIIGSLESEDFADY
YCLQYASSPLTFGAGTKLELKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	93	93
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCASYGSSYWYFDV
WGTGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSHKFMSTSVGDRVSITCKASQ
DVGTAVAWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDFTLTISNVQSED
LADYFCQQYSSYPFTFGSGTKLEIKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	94	94
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCASYYGSSRSYWYLDV
WGAGTTVTVSSGGGGSGGGGSGGGGSSIVMTQTPKFLLVSAGDRVTITCKASQS
VSNDVAWYQQKPGQSPKLLIYYASNRYTGVPDRFTGSGYGTDFTFTISTVQAEDL
AVYFCQQDYTSLPTFGAGTKLEIKR
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	95	95
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARQNDSSWAWFAY
WGQGTLVTVSAGGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVTIRCITSTDI
DDDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENTLSEDVA
DYYCLQSDNMPLTFGAGTKLELKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	96	96
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCALPYSNYGWYFD
VWGTGTTVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQ
DISNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIAT
YFCQQGNTLPFTFGSGTKLEIKR
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	97	97
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSYWYFDV
WGTGTTVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQG
ISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATY
YCQQYSKLPYTFGGGTKLEIKR
EVQLQQSGAELVKPGASVKLSCTASGFNIKDYYMHWVKQRTEQGLEWIGRIDPE	98	98
DGETKYAPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCAAYGNSAWFAYWG
QGTLVTVSAGGGGSGGGGSGGGGSDIVMTQSPATLSVTPGDRVSLSCRASQSIS
DYLHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGSDFTLSINSVEPEDVGVYYC
QNGHSFPWTFGGGTKLEIKR
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVRQAPGKGLEWMGWIN	99	99
TNTGEPTYAEEFKGRFAFSLETSASTAYLQINNLRNEDTATYFCARWYPYFDYWGQ
GTTVTVSSGGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVKN
LNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYTLTISNLESEDFATYYCLQ
FYEFPYTFGGGTKLEIKR
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	100	100
TNTGEPTYAEEFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARWYPYFDYWGQ
GTTLTVSSGGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVKN
LNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYYCL
QFYEFPYTFGGGTKLEIKR
QVQLQQSGAELAKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGYINP	101	101
SSGYTKYNQKFKDKATLTADKSSSTAYMQLSSLTYEDSAVYYCARSDGSSGNWYF
DVWGTGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRAS
GNIHNYLAWYQQKQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINSLQPE
DFGSYYCQHFWSTPWTFGGGTKLEIKR
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAG	102	102
GSTNYNSALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCAREGGYTGYFDVW
GAGTTVTVSSGGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAVT
TSNYANWVQEKPDHLFTGLIGGTSYRAPGVPVRFSGSLIGDKAALTITGAQTEDDA
MYFCALWYSTHYVFGGGTKVTVLR
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	103	103
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAYSNYVPYYAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASLGERVSLTCRASQE
ISGYLSWLQQKPDGTIKRLIYAASTLDSGVPKRFSGSRSGSDYSLTISSLESEDFADYY
CLQYASYPWTFGGGTKLEIKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	104	104
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAM
DYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVMTQSPATLSVTPGDRVSLSCRA
SQSISDYLHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGSDFTLSINSVEPEDV
GVYYCQNGHSFPYTFGGGTKLEIKR
EVQLQQSGAELVRPGALVKLSCKASGFNIKDYFMHWVKQRPEQCLEWIGWIDPE	105	105
TDNTIYDPKFQGKASITADTSSNTAYLQLSSLTSEDTAVYYCARSGNMGFTYWGQ
GTLVTVSAGGGGSGGGGSGGGGSENVLTQSPAIMSASLGEKVTMSCRASSSVNY
MYWYQQKSDASPKLWIYYTSNLAPGVPARFSGSGSGNSYSLTISSMEGEDAATYY
CQQFTSSPSTFGCGTKLEIKR
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKCLEWVATISSGG	106	106
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCASQGGSSWGAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSETTVTQSPASLSMAIGEKVTIRCITNTDI
DDDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENMLSEDVA
DYYCLQSDNLPLTFGCGTKLELKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKCLEWLGVIWSG	107	107
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARKGYGYDWYFDVW
GTGTTVTVSSGGGGSGGGGSGGGGSQLVLTQSSSASFSLGASAKLTCTLSSQHSTY
TIEWYQQQPLKPPKYVMELKKDGSHSTGDGIPDRFSGSSSGADRYLSISNIQPEDE
AIYICGVGDTIKEQFVYVFGCGTKVTVLG
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQCLEWIGEIDP	108	108
SDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSSYYYYAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSS
VSYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAA
TYYCQQWSSNPLTFGCGTKLELKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	109	109
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LHYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISFKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	110	110
GSTNYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLNWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	111	111
DSTSYNEKFKGKTTFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATAYTFSIYWIEWVKQRPGHGLEWIGEILPGS	112	112
GSTNYNEKVKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDY
WGQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	113	113
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
PQYVESPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	114	114
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKMSCKATGYTFSNYWIEWVKQRPGHGLEWIGEILP	115	115
GSGSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDY
WGQGSTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVQQRPGHGLEWIGEILPG	116	116
SGYTSYIEQFKGKATFTADTSSNTAYMQLGSLTSEDSAVYYCARRGYGYDEGFDY
WGQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFHQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	117	117
GSTSYNEKFKDKATFTADTSSNTAFMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPLTFGGGTKLEIK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEVLPG	118	118
SGSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDY
WGQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NGYLSWFQQKPGKSPQTLLYRANRLVDGVPSRFRGSGSGQDYSLTISSLEYEDMGI
YYCLQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKGTGYTFSSYWIEWVKQRPGHGLEWIGEISPGS	119	119
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINS
YLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYC
LQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFGTYWIEWVKQRPGHGLEWIGEILPG	120	120
SGTPNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDAGFDY
WGQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGF
YYCLQYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISFKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	121	12.
GSTSCNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSIYASLGERVTITCKASQDINSY
LNWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCL
QYDEFPPTFGVGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	122	122
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINSY
LSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCL
QYDEFPPTFGAGTKLELK
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	123	123
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINSY
LSWFQQKPGKSPKTLIYRAKRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCL
QYDEFPPTFGAGTKLELK
QVQLKQSGPGLVQPSQSLSITCTVSGFSLSSYGVHWVRQSPGKALEWLGVIWRG	124	124
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDIN
SYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYY
CLQYDEFPPTFGAGAKLELK
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTSYGVHWVRQSPGKGLEWLGVIWRG	125	125
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDSAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
VTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYPFTFGSGTKLEIK
QVQLKQSGPGPVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWRG	126	126
GSTDNNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
VTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYPFTFGSGTKLEIK
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTRYGVHWVRQSPGKGLEWLGVIWRG	127	127
GSTDHNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
VTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYPFTFGSGTKLEIK
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTTYGVHWVRQSPGKGLEWLGVIWRG	128	128
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
VTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYPFTFGSGTKLEIK
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTSYGVHWVRQSPGKGLEWLGVIWRG	129	129
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
VTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYLIHVRFGSGTKLEIK
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTRYGVHWVRQSPGKGLEWLGVIWRG	130	130
GSTDHNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSSGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
VTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYLIHVRFGSGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	131	131
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAY
WGQGTLVTVSAGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSV
SYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAAT
YYCQQWSSNPLYTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	132	132
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAY
WGQGTLVTVSAGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSV
SYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAAT
YYCQQWSSNPHVHVFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTTYWMHWVKQRPGQGLEWIGMIH	133	133
PNSDNTNYNEKFKSKATLTVDKSSSTAYIQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSAGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVS
YMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAATY
YCQQWSSNPLYTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	134	134
PNSGNTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAY
WGQGTLVTVSAGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSV
SYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAAT
YYCQQWSSNPLYTFGGGTKLEIK
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	135	135
SGSTYYNEKFKGKATLTADKSSNTVYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGAGTKLELK
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	136	136
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGAGTKLELK
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPG	137	137
SGSSYYNEKFRGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPQLLIYAASNLQSGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGAGTKLELK
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQKTGQGLEWIGEIYPG	138	138
SGSSYYNEKFKGKATLTADKSSNTAYIQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFGGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNEDPLTFGAGTKLELK
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	139	139
PSDSETHYNQMFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDGYYRFAY
WGQGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPSSLSASLGGKVTITCKASQDI
NKYIAWYQHKPGKGPRLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIATYY
CLQYDILMYTFGGGTKLEIK
QVQLQQPGAELVRPGASVRLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	140	140
PSDSETHFNQMFKDKATLTVDKSSSTAYMQVSSLTSEDSAVYYCATYDIYYRFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPSSLSASLGGKVTITCKASQDINK
YIAWYQHKPGKGPRLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIATYYCL
QYDILMYTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	141	141
PNSDSTNYNEKFKSKATLTVDKSSSTAYMHLSSLTSEDSAVYYCARPGGYGFADW
GQGTLVTVSAGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIV
KNLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYY
CLQFYEFPLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTTYWMHWVKQRPGQGLEWIGMIH	142	142
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFTYWG
QGTLVTVSAGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVK
NLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYYC
LQFYEFPLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	143	143
PNSGSPNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFAYW
GQGTLVTVSAGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIV
KNLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYY
CLQFYEFPLTFGAGTKLELK
QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWINWVKQRPGQGLEWIGNIYPS	144	144
DSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRGNYIDYWGQGT
TLTVSSGGGSGGGGSGGGGSENVLTQSPAIMSASLGEKVTMSCRASSSVNYMY
WYQQKSDASPKLWIYYTSNLAPGVPARFSGSGSGNSYSLTISSMEGEDAATYYCQ
QFTSSHTFGGGTKLEIK
QVQLQQPGAELVRPGASVKLSCKASGYTFTDYWINWVKQRPGQGLEWIGNIYPS	145	145
DSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRGNYIDYWGQGT
TLTVSSGGGSGGGGSGGGGSENVLTQSPAIMSASLGEKVTMSCRASSSVNYMY
WYQQKSDASPKLWIYYTSNLAPGVPARFSGSGSGNSYSLTISSMEGEDAATYYCQ
QFTSSHTFGGGTKLEIK
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	146	146
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDG
DSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAAT
YYCQQSNKDPLTFGAGTKLELK
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	147	147
SGSNYYNEKFKGKAIMTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWG
QGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNEDPLTFGAGTKLELK
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	148	148
SGSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDG
DSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAAT
YYCQQSNKDPFTFGAGTKLELK
QVQLKESGPGLVAPSQSLSITCTVSGFSLTNYGVHWVRQPPGKGLEWLGVVWAG	149	149
GITNYNWALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARGDGYDDGYAM
DYWGQGTSVTVSSGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASQ
SVSTSSYSYMHWYQQKPGQAPKLLIKYASNLESGVPARFSGSGSGTDFTLNIHPVE
EEDTATYYCQHSWEIPLTFGAGAKLELK
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVLWAG	150	150
GITNYNSALMSRLSIRKDNSKSQVFLKMYSLHTDDTAMYYCARGDGYDDGYAMD
YWGQGTSVTVSSGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASQS
VSTSSYSYMHWYQQKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLNVHPVE
EEDTATYYCQHSWEIPLTFGAGTKLELK
QVQLQQSGPQLVSPGASVKISCKASGYSFTSYWMYWVKQRPGQGLEWIGMIDP	151	151
SDSETRLNQKFKDRATLTVDKSSSTAYMQLSSPTSEDSAVYYCARTRNYWGQGTT
LTVSSGGGSGGGGSGGGGSDIQMTQTPSSLSASLGDRVTISCRASQDISNYLNWY
QQKPDGTVKLLIYSTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTL
PWTFGGGTKLEIK
QVQLQQSGPQLVSPGASVKISCKASGYSFTSYWMYWVKQRPGQGLEWIGMIDP	152	152
SDSETRLNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCARTRNYWGQGTT
LTVSSGGGSGGGGSGGGGSDIQMTQTPSSLSASLGDRVTISCRASQDISNYLNWY
QQKPDGTVKLLIYSTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNA
LPWTFGGGTKLEIK
QVQLQQSGPQLVSPGASVKISCKASGYSFTSYWMYWVKQRPGQGLEWIGMIDP	153	153
SDSETRLNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCARTRNYWGQGTS
LTVSSGGGSGGGGSGGGGSDIQMTQTPSSLSASLGDRVTISCRASQDISNYLNWY
QQKPDGTVKLLIYSTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTL
PWTFGGGTKLEIK
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	154	154
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSAMDY
WGQGTSVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAV
TTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTEDD
AMYFCALWYSTHYVFGGGTKVTVL
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYIHWVKQRPEQGLEWIGWIDPEN	155	155
GDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSSMDYW
GQGTSVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAVTT
SNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTEDDA
MYFCALWYSTHYVFGGGTKVTVL
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	156	156
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNVALLRYSSAMDY
WGQGTSVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAV
TTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTEDD
AMYFCALWYSTHYVFGGGTKVTVL
QVQLQQSGAELVKPGASVKLSCKASGYTFSNYYVYWVKQRPGQGLEWIGEINPS	157	157
NGDTNFNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYFCTSYYTHEAYYYAMD
CWGQGTSVTVSSGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVTIRCITSTDI
DDDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENTLSEDVA
DYYCLQSDNMPFTFGSGTKLEIK
QVQLQQSGAELVRPGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGRIDPE	158	158
DGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCTPYSIYDAMDYWG
QGTSVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAVTTS
NYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTEDDAM
YFCALWYSTHYFGGGTKVTVL
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	159	159
SGSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYW
GQGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPLTFGAGTKLELK
QVQLQQSGAELVRPGVSVKISCKGSGYSFTDYGMHWVKQSHAKSLEWIGVISTYY	160	160
GDASYNQKFKGKATMTVDKSSSTAYMELARLTSEDSAIYYCARQMDYDYTYYYA
MDYWGQGTSVTVSSGGGSGGGGSGGGGSDIVMSQSPSSLAVSVGEKVTMSCK
SSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLT
ISSVKAEDLAVYYCQQYYSYPPWTFGGGTKLEIK
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWNGEIYPG	161	161
SGSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARMDGPWFAYWG
QGTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYD
GDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDA
ATYYCQQSNEDPPTFGGGTKLEIK
QVTLKVSGPGILQPSQTLGLACTFSGISLSTSGMGLSWLRQPSGKALEWLASIWN	162	162
NDNYYNPSLKSRLTISKETSNNQVFLKLTSVDTADSTTYYCAWRPYYRYDSFAYWG
QGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPASLAASVGETVTITCRASENIYYS
LAWYQQKQGKSPQLLIYNANSLEDGVPSRFSGSGSGTQYSMKINSMQPEDTATY
FCKQAYDVPYTFGGGTKLEIK
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	163	163
TGGTAYNQKFKVKAILTADKSSSTAYMELRSLTSEDSAVYYCTRLGDYDVMDYWG
QGTSVTVSSGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDISNY
LNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQ
QDNTLPRTFGGGTKLEIK
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEID	164	164
PSDSYTNYNQKFKGKSTLTVDKSSSTAYMQLSSLTSEDSAVYYCARAGRYGSSFDY
WGQGTTLTVSSGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIS
NYLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYF
CQQGNTLPWTFGGGTKLEIK
QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPSGKGLEWLAHIYWD	165	165
DDKRYNPSLKSRLTISKDTSRNQGFLKITSVDTADTATYYCAGRPDDYDGAWFPY
WGQGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENI
YSNLAWYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFG
SYYCQHFWGTPWTFGGGTKLEIK
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	166	166
SGSNYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCAREEKIYFDYWGQG
TTLTVSSGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDGDS
YMNWYRQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYY
CQQSNEDPWTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	167	167
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARYDGYWFDYW
GQGTTLTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSSTGAVTT
SNYANWVQEKPDHLFTGLIGGTNNRAPGVPARFSGSLIGDKAALTITGAQTEDEAI
YFCALWYSNHWVFGGGTKLTVL
EVQLQQSGTVLARPGASVKMSCKTSGYTFTSYWMHWIKQRPGQGLEWIGAIYP	168	168
GNSDTTYNQKFKGKAKLTAVTSASTAYMELSSLTNEDSAVYYCTSLITTAYYFDYW
GQGTTLTVSSGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVK
NLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYYC
LQFYEFPLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	169	169
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAPETGDYGSSYV
WYFDVWGTGTTVTVSSGGGSGGGGSGGGGSQLVLTQSSSASFSLGASAKLTCTL
SSQHSTYTIEWYQQQPLKPPKYVMELKKDGSHSTGDGIPDRFSGSSSGADRYLSIS
NIQPEDEAIYICGVGDTIKEQFVFVFGGGTKVTVL
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	170	170
SGSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARGKVTRFAYWGQ
GTLVTVSAGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDG
DSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAAT
YYCQQSNEDPPTFGGGTKLEIK
EVQLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISDGG	171	171
SYTYYPDNVKGRFTISRDNAKNNLYLQMSHLKSEDTAMYYCARDQDSNWEYFDY
WGQGTSLTVSSGGGSGGGGSGGGGSDIQMTQSPSSLSASLGERVSLTCRASQDI
GISLNWLQQEPDGTIKRLIYATSSLDSGVPKRFSGSRSGSDYSLTISSLESEDFVDYYC
LQYASSPYTFGGGTKLEIK
QIQLVQSGPELKKPGETVKISCKASGYTFTDYSMHWVRQAPGKGLKWMAWINTE	172	172
TGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARESWDRAMDYWG
QGTSVTVSSGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASENIYSYL
AWYQQKQGKSPQLLVYNAKNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGYYCQ
HFWGTPYTFGGGTKLEIK
QVQLQQSGPQLVSPGASVKISCKASGYSFTNYWMHWVKQRPGQGLEWIGMID	173	173
PSDSETRLNQQFKDKATLTVDESSSTAYMQLSSPTSEDSAVYYCAIPYYAMDYWG
QGTSVTVSSGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDINSY
LSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCL
QYDEFPLTFGAGTKLELK
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	174	174
NSGNTNYNEKNKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCATYYGNYVWYFD
VWGAGTSVTVSSGGGSGGGGSGGGGSDIQMTQSPSSLSASLGERVSLTCRASQD
IHGYLNLFQQKPGETIKHLIYETSNLDSGVPKRFSGSRSGSDYSLIIGSLESEDFADYY
CLQYASSPLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	175	175
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCASYGSSYWYFDV
WGTGTTVTVSSGGGSGGGGSGGGGSDIVMTQSHKFMSTSVGDRVSITCKASQD
VGTAVAWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDFTLTISNVQSEDL
ADYFCQQYSSYPFTFGSGTKLEIK
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGALYS	176	176
GNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSHLWY
FDVWGAGTTVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSST
GAVTTSNYANWVQEKPDHLFTGLIGGTNNRAPGVPARFSGSLIGDKAALTITGAQ
TEDEAIYFCALWYSNHLVFGGGTKLTVL
QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPSGKGLEWLAHIYWD	177	177
DDKRYNPSLKSRLTISKDTSRNQVFLKITSVDTADTATYYCARRAHYDYGWYFDVW
GAGTTVTVSSGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYVASNLESGIPARFRGSGSGTDFTLNIHPVEEED
AAIYYCQQSHEDPRTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	178	178
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAGYDYDWYFDV
WGTGTTVTVSSGGGSGGGGSGGGGSENVLTQSPAIMSASPGEKVTMTCSASSSV
SYMHWYQQKSSTSPKLWIYDTSKLASGVPGRFSGSGSGNSYSLTISSMEAEDVAT
YYCFQGSGYPLTFGAGTKLELK
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	179	179
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARHEDSNYHYFDYW
GQGTTLTVFSGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYS
NLAWYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSY
YCQHFWGTPYTFGGGTKLEIK
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	180	180
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARQNDSSWAWFAY
WGQGTLVTVSAGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVTIRCITSTDID
DDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENTLSEDVADY
YCLQSDNMPLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	181	181
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCALPYSNYGWYFD
VWGTGTTVTVSSGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQD
ISNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATY
FCQQGNTLPFTFGSGTKLEIK
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	182	182
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSYWYFDV
WGTGTTVTVSSGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIS
NYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYYC
QQYSKLPYTFGGGTKLEIK
EVQLQQSGAELVKPGASVKLSCTASGFNIKDYYMHWVKQRTEQGLEWIGRIDPE	183	183
DGETKYAPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCAAYGNSAWFAYWG
QGTLVTVSAGGGSGGGGSGGGGSDIVMTQSPATLSVTPGDRVSLSCRASQSISDY
LHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGSDFTLSINSVEPEDVGVYYCQ
NGHSFPWTFGGGTKLEIK
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAG	184	184
GSTNYNSALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCAREGGYTGYFDVW
GAGTTVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAVTT
SNYANWVQEKPDHLFTGLIGGTSYRAPGVPVRFSGSLIGDKAALTITGAQTEDDA
MYFCALWYSTHYVFGGGTKVTVL
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	185	185
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAYSNYVPYYAMDY
WGQGTSVTVSSGGGSGGGGSGGGGSDIQMTQSPSSLSASLGERVSLTCRASQEIS
GYLSWLQQKPDGTIKRLIYAASTLDSGVPKRFSGSRSGSDYSLTISSLESEDFADYYC
LQYASYPWTFGGGTKLEIK
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPG	186	186
SGSAYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGFDYWGQGTT
LTVSSGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSY
MNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYC
QQSNEDPLPTFGAGTQRELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	187	187
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSGYGYYF
DYWGQGTTLTVSSGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASS
SVSYMHWYQQKSGTSPKRWIYDTSKLASGVPVRFSGSGSGTSYSLTISSMEAEDA
ATYYCQQWSSNPLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	188	188
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSYGWY
FDVWGTGTTVTVSSGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRAS
GNIHNYLAWYQQKQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINSLQPE
DFGSYYCQHFWSTPWTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	189	189
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSYGWY
FDVWGTGTTVTVSSGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRAS
ENIYSYLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPED
FGSYYCQHHYGTPFTFGSGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	190	190
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCASDYYGSSYGWY
FDVWGTGTTVTVSSGGGSGGGGSGGGGSENVLTQSPAIMSASLGEKVTMSCRA
SSSVNYMYWSQQKSDASPKLWIYYTSNLAPGVPPRFSGSGSGNSYSLTISSMEGE
DAATYYCQQFTSSLTFGAGTKLELK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	191	191
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSYGWY
FDVWGTGTTVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSST
GAVTTSNYANWVQEKPDHLFTGLIGSTNNRAPGVPARFSGSLIGDKSALTITGAQT
EDEAIYFCTLWYSNHWVFGGGTKLTVL
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	192	192
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRDYYGSGYGWY
FDVWGTGTTVTVSSGGGSGGGGSGGGGSDIVMTQSHKFMSTSVGDRVSITCKA
SQDVGTAVAWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDFTLTISNVQS
EDLADYFCQQYSSYPFTFGSGTKLEIK
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	193	193
PSDSETHYNQMFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDGYYRFAY
WGQGTLVTVSAGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELK
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	194	194
PSDSETHFNQMFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDVYYRFAY
WGQGTLVTVSAGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENI
YSNLAWYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFG
SYYCQHFWGTPFTFGSGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	195	195
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAM
DYWGQGTSVTVSSGGGSGGGGSGGGGSDIVMTQSPATLSVTPGDRVSLSCRAS
QSISDYLHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGSDFTLSINSVEPEDVG
VYYCQNGHSFPYTFGGGTKLEIK
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIH	196	196
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAM
DYWGQGTSVTVSSGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSSTG
AVTTSNYANWVQEKPDHLFTGLIGGTNNRAPGVPARFSGSLIGDKAALTITGAQT
EDEAIYFCALWYSNHWVFGGGTKLTVL
EVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	197	197
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASQLTGTWYYFDYW
GQGTTLTVSSGGGSGGGGSGGGGSEIFVTQSPASLSMAIGEKVTIRCITSTDIDDD
MNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENMLSEDVADYY
CLQSDNLPLTFGAGTKLELK
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	198	198
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASQLTGTWYYFDYW
GQGTTLTVSSGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTITCSASSSVSY
MHWFQQKPGTSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISRMEAEDAATYY
CQQRSSYPPTFGSGTKLELK
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	199	199
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASQLTGTWYYFDYW
GQGTTLTVSSGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSY
MHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAATYY
CQQWSSNPLTFGSGTKLEIK
DVKLVESGGGLVKLGGSLKLSCAASGFTFSNYYMSWVRQTPEKRLELVAVINSNG	200	200
GSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTALYYCARQEGIGYAMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTLTCSASSSVSSS
YLYWYQQKPGSSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISSMEAEDAASYFC
HQWSSYPPTFGAGTKLELKR
EVQLQQSGPELVKPGASVKISCKTSGYTFTEYTMHWVKQSHGKSLEWIGGIYPNN	201	201
GGTSYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARGGWLLGYWGQG
TTLTVSSGGGGSGGGGSGGGGSQLVLTQSSSASFSLGASAKLTCTLSSQHSTYTIE
WYQQQPLKPPKYVMELKKDGSHSTGDGIPDRFSGSSSGADRYLSISNIQPEDEAIYI
CGVGDTIKEQFVYVFGGGTKVTVLR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	202	202
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARDGGIRGAMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSDVLMTQTPLSLPVSLGDQASISCRSSQSIVH
SNGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDL
GVYYCFQGSHVPWTFGGGTKLEIKR
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	203	203
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSDIKMTQSPSSMYASLGERVTITCKASQDI
NSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIY
YCLQYDEFPPTFGAGTKLELKR
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	204	204
TGGTAYNQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRNYDYAMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSDVVMTQTPLTLSVTIGQPASISCKSSQSLLD
SDGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDL
GVYYCWQGTHFPWTFGGGTKLEIKR
DVKLVESGGGLVKLGGSLKLSCAASGFTFSSYYMSWVRQTPEKRLELVAVINSNGG	205	205
STFYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTALYYCARQEGIGYALDYWGQG
TSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTLPCSASSSVSSSYL
YWYQQKPGSSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISSMEAEDAASYFCH
QWSSYPPTFGAGTKLELKR
EVKLVESGGDLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVAAISSGG	206	206
STYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCAREREWGVYYGSSLDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDVLMTQTPLSLPVSLGDQASISCRSSQS
IVYSNGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEA
EDLGVYYCFQGSHVPPTFGGGTKLEIKR
EVQLQQSGAELVKPGASVKLSCTASGFNIKDTYMHWVKQRPEQGLEWIGRIDPA	207	207
NGNTKYDPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCARSDGNYDWGQGT
LVTVSAGGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIYNNLA
WYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQ
HFWGTPWTFGGGTKLEIKR
DVKLVESGGGLVKLGGSLKLSCAASGFTFSNYYMSWVRQTPEKRLELVAVINSNG		208
GSTYYPDTVKGRFTISRDNAKNILYLQMSSLKSEDTALYYCARQEGIGYGMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTLTCSASSSVSSS
YLYWYQQKPGSSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISSMEAEDAASYFC
HQWSSYPPTFGAGTKLELKR
EVQLVESGGGLVQPKGSLKLSCAASGFTFNTYVMNWVRQAPGKGLEWVARIRSK	209	209
SDNYATYYADSVKDIFTISRDDSQSMLYLQMNNLKTEDTAMYYCVRHDGVVGFD
VWGAGTTVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSAS
SSVSYMYWYQQKPGSSPRLLIYDTSNLASGVPVRFSGSGSGTSYSLTISRMEAEDA
ATYYCQQWSTYPPITFGAGTKLELKR
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYD	210	210
GSNNYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCARGGGRGWGQGTLV
TVSAGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSYMYWY
QQKPGSSPRLLIYDTSNLASGVPVRFSGSGSGTSYSLTISRMEAEDAATYYCQQWS
SYPFTFGSGTKLEIKR
QIQLVQSGPELKKPGETVKISCKASGYTFTDYSMHWVKQAPGKGLKWMGWINT	211	211
ETGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARDYYDYYYAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQIVLSQSPAILSASPGEKVTMTCRASSS
VSYMHWYQQKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAA
TYYCQQWSSNPYTFGGGTKLEIKR
QIQLVQSGPELKKPGETVKISCKASGYTFTDYSMHWVKQAPGKGLKWMGWINT	212	212
ETGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARESWDRAMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSDIQMTQSPASLSVSVGETVTITCRASENIY
SNLAWYQQKQGKSPQLLVYAATNLADGVPSRFSGSGSGTQYSLKINSLQSEDFGS
YYCQHFWGTPWTFGGGTKLEIKR
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPEQGLEWIGRIDP	213	213
YDSETHYNQKFKDKAILTVDKSSSTAYMQLSSLTSEDSAVYYCARIYSDYDGAWFA
YWGQGTLVTVSAGGGGSGGGGSGGGGSDIVMTQSHKFMSTSVGDRVSITCKAS
QDVSTAVAWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDYTLTISSVQAE
DLALYYCQQHYSTPWTFGGGTKLEIKR
EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMDWVKQSHGESFEWIGRVNP	214	214
YNGGTSYNQKFKGKATLTVDKSSSTAYMELNSLTSEDSAVYYCARGTVGFAYWGQ
GTLVTVSAGGGGSGGGGSGGGGSDVVMTQTPLTLSVTIGQPASISCKSSQSLLDS
DGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLG
VYYCWQGTHFPWTFGGGTKLEIKR
EVKLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVASISSGGS	215	215
TYYPDSVKGRFTISRDNARNILSLQMSSLRSEDTAMYYCAREREWGVFYGSSLDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDVLMTQTPLSLPVSLGDQASISCRSSQS
IVHSNGNTYLEWYLQKPGQSPKFLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEA
EDLGVYYCFQGSHVPPTFGGGTKLEIKR
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWIRQTPEKRLEWVATISSGG	216	216
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHDDSSYGYFDYW
GQGTTLTVSSGGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVTIRCITSTDIDD
DMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENTLSEDVADYY
CLQSDNMPLTFGGGTKLEIKR
EVKLVESGGGLVKPGGSLKLSCAASGFTFSNYAMSWVRQTPEKRLEWVASISSGG	217	217
TTYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCARTMPDVWGAGTTVT
VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQ
HKPGKGPRLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDNLY
MYTFGGGTKLEIKR
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAG	218	218
GSTNYNSALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARDTDGYYWAMD
YWGQGTSVTVSSGGGGSGGGGSGGGGSDIQMNQSPSSLSASLGDTITITCHASQ
NINVWLSWYQQKPGNIPKLLIYKASNLHTGVPSRFSGSGSGTGFTLTISSLQPEDIA
TYYCQQGQSYPYTFGGGTKLEIKR
DVQLQESGPGLVKPSQSLSLTCTVTGYSITSDHAWNWIRQFPGNKLEWMGYISYS	219	219
GSTTYNPSLKSRISITRDTSKNQFFLQLNSVTTEDTATYYCARKWGDYWGQGTSVT
VSSGGGGSGGGGSGGGGSQIVLTQSPALMSASPGEKVTMTCSASSSVSYMYWY
QQKPRSSPKPWIYLTSNLASGVPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWS
SNPPTFGGGTKLEIKR
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	220	220
TGGTAYNQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRNYDYALDYWGQ
GTSVTVSSGGGGSGGGGSGGGGSDVVMTQTPLTLSVTIGQPASISCKSSQSLLDS
DGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLG
FYYCWQGTHFPWTFGGGTKLEIKR
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYD	221	221
GSNDYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCARGGGRGWGQGTLV
TVSAGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASLSVSDMYW
YQQKPGSSPRLLIYDTSNLASGVPVRFSGSGSGTSYSLTISRMEAEDAATYYCQQW
SSYPFTFGSGTKLEIKR
DVKLVESGGGLVKLGGSLKLSCAASGFTFSNYYMSWVRQTPEKRLELVAVINSNG	222	222
GSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTALYYCARQEEIGYAMDYWG
QGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTLTCSASSSVSSS
YLYWYQQRPGSSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISSMEAEDAASYFC
HQWSSYPPTFGAGTKLELKR
EVQLQQSGAELVRPGALVKLSCKASGFNIKDYFMHWVKQRPEQGLEWIGWIDPE	223	223
TDNTIYDPKFQGKASITADTSSNTAYLQLSSLTSEDTAVYYCARSGNMGFTYWGQ
GTLVTVSAGGGGSGGGGSGGGGSENVLTQSPAIMSASLGEKVTMSCRASSSVNY
MYWYQQKSDASPKLWIYYTSNLAPGVPARFSGSGSGNSYSLTISSMEGEDAATYY
CQQFTSSPSTFGGGTKLEIKR
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	224	224
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCASQGGSSWGAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSETTVTQSPASLSMAIGEKVTIRCITNTDI
DDDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENMLSEDVA
DYYCLQSDNLPLTFGAGTKLELKR
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISNG	225	225
GSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHEITTRFAYWG
QGTLVTVSAGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDY
DGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEED
AATYYCQQSNEDPWTFGGGTKLEIKR
VQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYMSYD	226	226
GSNNYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCAREAGYFDYWGQGTT
LTVSSGGGGSGGGGSGGGGSDIVLTQSPATLSVTPGDSVSLSCRASQSISNNLHW
YQQKSHESPRLLIKYASQSISGIPSRFSGSGSGTDFTLSINSVETEDFGMYFCQQSNS
WPFTFGSGTKLEIKR
EVQLVESGGGLVQPKGSLKLSCAASGFSFNTYAMNWVRQAPGKGLEWVARIRSK	227	227
SNNYATYYADSVKDRFTISRDDSESMLYLQMNNLKTEDTAMYYCVRQYGYDFDY
WGQGTTLTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTLTCSASSSV
SSSYLYWYQQKPGSSPKLWIYSTSNLASGVPARFSGSGSGTSYSLTISSMEAEDAAS
YFCHQWSSYPPTFGGGTKLEIKR
EVQLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	228	228
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARHKGVNWDYFDY
WGQGTTLTVSSGGGGSGGGGSGGGGSETTVTQSPASLSVATGEKVTIRCITSTDI
DDDMNWYQQKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENTLSEDVA
DYYCLQSDNMPLTFGAGTKLELKR
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	229	229
TGGTAYNQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRGDGNYDSWYFD
VWGAGTTVTVSSGGGGSGGGGSGGGGSDVVMTQTPLTLSVTIGQPASISCKSSQ
SLLDSDGKTYLHWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVE
AEDLAVYYCWQGTHFPWTFGGGTKLEIKR
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	230	230
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARLPVTTVVFDYWG
QGTTLTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASLGGKVTITCKASQDINK
YIAWYQHKPGKGPRLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIATYYCL
QYDNLRTFGGGTKLEIKR
EVQLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	231	231
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARRPVVVPFDYWGQ
GTTLTVSSGGGGSGGGGSGGGGSQAVVTQESALTTSPGETVTLTCRSSTGAVTTS
NYANWVQEKPDHLFTGLIVGTNNRAPGVPARFSGSLIGDKAALTITGAQTEDEAIY
FCVLWYSNHLVFGGGTKLTVLG
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	232	232
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARGWDADYFDYWG
QGTTLTVSSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLSCKASENV
GTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLAD
YHCGQSYSYPPTFGAGTKLELKR
QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWMHWVKQRPGQGLEWIGMIH	233	233
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRYDYDDYWGQ
GTTLTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASETVDSYG
YSFMHWYQQKPGQPPKLLIYRASNLESGIPARFSGSGSRTDFTLTINPVEADDVAT
YYCQQSNEDPRTFGGGTKLEIKR
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGDINPN	234	234
NGGTSYNQKFKGKATLTVDKSSSTAYMDLRSLTSEDSAVYYCARSELGLYAMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSDIVMSQSPSSLAVSVGEKVTMSCKSSQSL
LYSTNQKNYLAWYQQKPGQSPKLLLYWASTRESGVPDRFTGSGSGTDFTLTINSV
KAEDLAVYYCQQYYSYRTFGGGTKLEIKR
QVQLQQSGAELMKPGASVKLSCKATGYTFTGYWIEWVKQRPGHGLEWIGEILPG	235	235
SGSTNYNEKFKGKATFTADTSSNTAYMQLSSLTTEDSAIYYCARGRIHYFDYWGQG
TTLTVSSGGGGSGGGGSGGGGSDVVMTQTPLTLSVTIGQPASISCKSSQSLLDSD
GKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGV
YYCWQGTHFPFTFGSGTKLEIKR
QVQLQQSGAELMKPGASVKLSCKATGYTFTGYWIEWVKQRPGHGLEWIGEILPG	236	236
SGSTNYNEKFKGKATFTADTSSNTAYMQLSSLTTEDSAIYYCARGRIHYFDYWGQG
TTLTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCKASQSVDYDG
DSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAAT
YYCQQSNEDPFTFGSGTKLEIKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	237	237
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARKGYGYDWYFDVW
GTGTTVTVSSGGGGSGGGGSGGGGSQLVLTQSSSASFSLGASAKLTCTLSSQHSTY
TIEWYQQQPLKPPKYVMELKKDGSHSTGDGIPDRFSGSSSGADRYLSISNIQPEDE
AIYICGVGDTIKEQFVYVFGGGTKVTVLG
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEID	238	238
PSDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSSYYYYAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSS
VSYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAA
TYYCQQWSSNPLTFGAGTKLELKR
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYD	239	239
GSNNYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCARGGGRDWGQGTTLT
VSSGGGGSGGGGSGGGGSEIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWY
QQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEF
PLTFGAGTKLELKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	240	240
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARGGDYDSYAMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASESVD
NYGISFMNWFQQKPGQPPKLLIYAASNQGSGVPARFSGSGSGTDFSLNIHPMEE
DDTAMYFCQQSKEVPPTFGGGTKLEIKR
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYWITWVKQRPGQGLEWIGDIYP	241	241
GSGSTNYNEKFKSKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARESVYDGYSWYF
DVWGTGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPATLSVTPGDRVSLSCRA
SQSISDYLHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGSDFTLSINSVEPEDV
GVYYCQNGHSFPLTFGAGTKLELKR
EFQLQQSGPELVKPGASVKISCKASGYSFTDYNMNWVKQSNGKSLEWIGVINPNY	242	242
GTTSYNQKFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCASTYDYDDWYFDV
WGTGTTVTVSSGGGGSGGGGSGGGGSDVLMTQTPLSLPVSLGDQASISCRSSQS
IVHSNGDTYLEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEA
EDLGVYYCFQGSHVPLTFGAGTKLELKR
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEID	243	243
PSDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSGNYLYAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSS
VSYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAA
TYYCQQWSSNPLTFGAGTKLELKR
EFQLQQSGPELVKPGASVKISCKASGYSFTDYNMNWVKQSNGKSLEWIGVINPNY	244	244
GTTSYNQKFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCAREGTSWYFDVWG
TGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPTFLAVTASKKVTISCTASESLYSS
KHKVHYLAWYQKKPEQSPKLLIYGASNRYIGVPDRFTGSGSGTDFTLTISSVQVEDL
THYYCAQFYSYPYTFGGGTKLEIKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWRG	245	245
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKKGDGYDWYFDV
WGTGTTVTVSSGGGGSGGGGSGGGGSQLVLTQSSSASFSLGASAKLTCTLSSQHS
TYTIEWYQQQPLKPPKYVMELKKDGSHSTGDGIPDRFSGSSSGADRYLSISNIQPE
DEAIYICGVGDTIKEQFVYVFGGGTKVTVLG
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	246	246
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCAREGNYGSSYDAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASQS
VSTSSYSYMHWYQQKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLNIHPVEE
EDTATYYCQHSWEIPLTFGAGTKLELKR
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEID	247	247
PSDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSSNYPYAMDY
WGQGTSVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSS
VSYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAA
TYYCQQWSSNPLTFGAGTKLELKR
EVQLQQSVAELVRPGASVKLSCTASGFNIKNTYMHWVKQRPEQGLEWIGRIDPA	248	248
NGNTKYAPKFQGKATITADTSSNTAYLQLSSLTSEDTAIYYCAYYSGLYWGQGTLVT
VSAGGGGSGGGGSGGGGSDIQMTQSSSYLSVSLGGRVTITCKASDHINNWLAW
YQQKPGNAPRLLISGATSLETGVPSRFSGSGSGKDYTLSITSLQTEDVATYYCQQY
WSTPLTFGAGTKLELKR
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	249	249
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARRGQIYYGYSWFA
YWGQGTLVTVSAGGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASE
NIYSYLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDF
GSYYCQHHYGTPYTFGGGTKLEIKR
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGDINPN	250	250
NGGTSYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARSTVVADWYFDV
WGTGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPASLSASVGETVTITCRASEN
IYSYLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFG
SYYCQHHYGTPPTFGGGTKLEIKR
QVQLQQSGAELARPGASVKLSCKASGYTFTSYGISWVKQRTGQGLEWIGEIYPRS	251	251
GNTYYNEKFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCARSGSSYGYFDVWGT
GTTVTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSY
MHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAATYY
CQQWSSNPPTFGAGTKLELKR
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	252	252
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARKGGYDAYAMDYW
GQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPASLAVSLGQRATISCRASESVD
NYGISFMNWFQQKPGQPPKLLIYAASNQGSGVPARFSGSGSGTDFSLNIHPMEE
DDTAMYFCQQSKEVPPTFGGGTKLEIKR
EFQLQQSGPELVKPGASVKISCKASGYSFTDYNMNWVKQSNGKSLEWIGVINPNY	253	253
GTTSYNQKFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCAREGFITTVVAVDY
WGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQSPTFLAVTASKKVTISCTASESL
YSSKHKVHYLAWYQKKPEQSPKLLIYGASNRYIGVPDRFTGSGSGTDFTLTISSVQV
EDLTHYYCAQFYSYPYTFGGGTKLEIKR
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	254	254
TGGTAYNQKFKGKAILTADKSSSTAYMELRSLTSEDSAVYYCTREGNYDAMDYWG
QGTSVTVSSGGGGGGGGSGGGGSQAVVTQESALTTSPGGTVILTCRSSTGAVTT
SNYANWVQEKPDHLFTGLIGGTSNRAPGVPVRFSGSLIGDKAALTITGAQTEDDA
MYFCALWYSTHYVFGGGTKVTVLG
QVQLQQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDP	255	255
SDSYTNYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARWDYYGVDYW
GQGTTLTVSSGGGGSGGGGSGGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSIS
YMHWYQQKPGTSPKRWIYDTSKLASGVPARFSGSGSGTSYSLTISSMEAEDAATY
YCHQRSSYPTFGAGTKLELKR
EVQLVESGGGLVQSGGSLRLSCAASGFTFSGYWMYWVRQAPGKGLEWVSAISP	256	256
GGGSTYYPDSVKGRFTISRDNAKNTLYLQMNSLEPEDTALYYCASSLTATHTYEYDY
WGQGTQVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQCLEWMGWINP	257	9316
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGSYSD
WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSTPWTFGCGTKVEIKR
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQCLEWMGGIIPL	258	9317
SGAPNYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGALYNWNDGW
FDPWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SQDIGDYLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQANSFPLTFGCGTKVEIKR
QVQLVQSGAEVKKPGASVKVSCKASGYSLITHWMHWVRQAPGQCLEWMGMI	259	9318
NPSDGVTYYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREYYGEGFD
YWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QGISNYLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYSTPLTFGCGTKVEIKR
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSDHHVHWVRQAPGQGLEWMGGIIP	260	9319
IFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSSWYLHFQH
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
GIASYLAWYQQKPGKAPKLLIYAASTLQPGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQFDSYPITFGQGTKVEIKR
QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYGIAWVRQAPGQGLEWMGISYP	261	9320
SDGSTSSAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRLGDLDYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISS
WLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQGYSTPYIFGQGTKVEIKR
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYVHWVRQAPGQGLEWVGWIST	262	9321
FTGNTDYAQNFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDAPLAAAGTDY
YYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTI
TCRASQGISNYLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQSYNTPFTFGQGTRLEIKR
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYALSWVRQAPGQGLEWMGIINPS	263	9322
GGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDPGMDVW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDIS
NYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYY
CQQSYSTPLTFGQGTKVEIKR
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	264	9323
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGSYSD
WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSTPWTFGQGTKVEIKR
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYALSWVRQAPGQGLEWMGIINPS	265	9324
GGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDPGMDVW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDIS
NYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYY
CQQSYSTPLTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIIDPS	266	9325
GGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDMGMDV
WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
SISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQSYSTPLTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAFSWVRQAPGQGLEWMGIINP	267	9326
SGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVGDRGMDV
WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQ
DISNYLNWYQQKPGKAPKLLIYKASSLETGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQSFSSPLTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGSTFSGYYMHWVRQAPGQGLEWMGWI	268	9327
DPNGGGTQYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDIVHDGT
EYFQHWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
RASQNVNTWLAWYQQKPGKAPKLLIYEASSLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQANSFPFTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINP	269	9328
SGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDIVHDGTEYF
QHWGQGTLVTVSSGGGGGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SQSISDWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCAQHNHYPYTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	270	9329
GGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGRDHDAFDI
WGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQ
SVLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYTTPFTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGFTFTDYGISWVRQAPGQGLEWMGIINPS	271	9330
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGRSHDAFDIW
GQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSV
LSSSYNKNYLAWYQQKPGQPPKLLIYWASTRASGVPDRFSGSGSGTDFTLTISSLQ
AEDVAVYYCQQYYSTPFTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGW	272	9331
MNPHSGDTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARWVGTT
EYYYYYYMDVWGKGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGD
RVTITCRASQAIRDDLGWYQQKPGKAPKLLIYDASHLEAGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANSFPITFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYLHWVRQAPGQGLEWMGIIDPS	273	9332
GGSTSIAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATTAYYDFWSGYS
MDVWGKGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCR
ASQGVGNDLAWYQQKPGKAPKLLIYAASTLQTGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQQASSFPLTFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSHYMHWVRQAPGQGLEWMGIIDP	274	9333
SGGSTSYAQEFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDMDNWNTGY
YYYMDVWGKGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTI
TCRASQIIGTNLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQSYTFPVTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAINWVRQAPGQGLEWMGWVN	275	9334
PNSGDTAYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQRGGDA
WDVWGKGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCR
ASQSISTWLAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQSYSTPFTFGPGTKVDIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIITPS	276	9335
GGSTTYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDTAGHFDIWGQ
GTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSVLSS
SNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAED
VAVYYCQQYYGSPLTFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFRNDVINWVRQAPGQGLEWIGWMN	277	9336
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNPDLDGM
DVWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSS
QSVLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTIS
SLQAEDVAVYYCQQYYSSPPTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAINWVRQAPGQGLEWLGWISA	278	9337
YNGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLVGHFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSVL
SSSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQA
EDVAVYYCQQYYSSPPTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	279	9338
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGSYSD
WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSTPWTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGNTLSSHAISWVRQAPGQGLEWMGIINPS	280	9339
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGSSGTFDY
WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRASGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYGSPPTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYAISWVRQAPGQGLEWMGWINP	281	9340
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSTDVIDYW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDI
RNYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQAYSFPWTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYIFTSYDINWVRQAPGQGLEWMGWINP	282	9341
NSGDTKYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGGTVTPTEE
YYYYGMDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDR
VTITCQASQDISNYLNWYQQKPGKAPKLLIYNASNLETGVPSRFSGSGSGTDFTLTI
SSLQPEDFATYYCQQLNSYPFTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWISV	283	9342
YNGNTNYAQNLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASLDDLDYWGQ
GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQSISTW
LAWYQQKPGKAPKLLIYAASTLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCL
QHYTYPLTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGHTFTSYYIHWVRQAPGQGLEWMGWIN	284	9343
PNNGGTHYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDMVRDSAE
YFQHWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
RASEDISTYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQSHTIPWTFGQGTRLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFITSYIHWVRQAPGQGLEWMGMINPS	285	9344
GGTTTYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDSSGYPIDYWGQ
GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASHHISDF
LNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
QSYSSPYTFGQGTKLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGGIIPL	286	9345
SGAPNYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGALYNWNDGW
FDPWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SQDIGDYLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQANSFPLTFGGGTKVEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTVGSWYMSWVRQAPGKGLEWVAGIWY	287	9346
EGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLGTASLPYFDY
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
DIRSYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQSYTAPPTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWVGWIN	288	9347
PNRGDTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARESGDGFDP
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
DISNNLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCLQHNTYPLTFGQGTKLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTNYYIHWVRQAPGQGLEWMGWM	289	9348
NPNSGNTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWPNWFD
PWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QDISNWLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQAISFPLTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGYSFTDNYIHWVRQAPGQGLEWMGWIRS	290	9349
DNGETSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREVQLVGFDY
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
GIANYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQADSFPLTFGQGTKVEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSDHHVHWVRQAPGQGLEWMGGIIP	291	9350
IFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSSWYLHFQH
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
GIASYLAWYQQKPGKAPKLLIYAASTLQPGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQFDSYPITFGQGTKVEIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIYWVRQAPGQGLEWMGGIIPIF	292	9351
GTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKGVDRYNWNDAFD
YWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QGISNYLAWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSSIIPFTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWI	293	9352
HSNSGGTHSAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARESSGYDSS
LDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQAYSFPYTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYGISWVRQAPGQGLEWVGWINP	294	9353
NSGDTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTDPRLDSSDPG
YWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSIGRWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYSTPRTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFGNYGINWVRQAPGQGLEWMGWIS	295	9354
AYNGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGMDVWG
QGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSINS
WLAWYQQKPGKAPKLLIYDTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQTYSTPYTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYGIAWVRQAPGQGLEWMGISYP	296	9355
SDGSTSSAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRLGDLDYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISS
WLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQGYSTPYIFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMN	297	9356
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSIVGGYPF
DYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQTDSIPITFGQGTRLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGTITPI	298	9357
FGTTDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYSSSWHDDAF
DIWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSISSYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSYSIPYTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIIDPS	299	9358
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDYGLDSW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIR
SYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQTYTIPITFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGW	300	9359
MNPNSGDTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATGGSDSS
GYYYEGYFQHWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGD
RVTITCRASQTISNWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANSFPPTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWLGYMSP	301	9360
NSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDKGGYYDSS
GYYWYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTIT
CRASQYIGSYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQVDSYPLTFGGGTKVEIK
EVQLLESGGGLVQPGGSLRLSCAASGFSLSSYEMHWVRQAPGKGLEWVSAISSN	302	9361
GGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGDGDGYNPDF
DYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSS
QSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISR
VEAEDVGVYYCMQGTHWPPTFGQGTKLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWIDP	303	9362
TSGATDTAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKDPIVATEVDYW
GQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLL
HSNGYNYLDWYLQKPGQSPQLLIYFGSNRASGVPDRFSGSGSGTDFTLKISRVEAE
DVGVYYCMQALQAPVSFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMS	304	9363
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGAFDIW
GQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSV
LSSSYNKNYLAWYQQKPGQPPKLLIYWASSRQSGVPDRFSGSGSGTDFTLTISSLQ
AEDVAVYYCQQYYSTPLTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGVTISNYAISWVRQAPGQGLEWMGWMN	305	9364
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGLLDAFDI
WGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQ
SVSSSSYNKNYLAWYQQKPGQPPKLLIYWASVRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSTPITFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYGITWVRQAPGQGLEWMGWM	306	9365
NPYDGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGRHHDA
FDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCK
STQNVLSSSNNNSYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTL
TISSLQAEDVAVYYCQQYYSTPFTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	307	9366
GDGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDISNDAFDIW
GQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQD
IGNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQTYNTPLTFGGGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYILTGHYMHWVRQAPGQGLEWMGWIS	308	9367
AYNGDTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGSSWDDAF
DIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQA
SQDISNYLNWYQQKPGKAPKLLIYEASTLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQSYSTPFTFGPGTKVDIK
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNHYTSWVRQAPGKGLEWVSAIGAG	309	9368
GGTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCAREGWNDDVFDIW
GQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQD
ISTWLAWYQQKPGKAPKLLIYRASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQSYSIPLTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWVGIINPS	310	9369
AGTTYYAERFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGNFGAFDIWG
QGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQNIN
NYLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYY
CQQSYSAPVTFGQGTKLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTTYAITWVRQAPGQGLEWMGEIIPIF	311	9370
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDKSGWNYGSGSY
NDAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTI
TCRASQNINTWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQAYSFPFTFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGYAFTGYYMHWVRQAPGQGLEWMGW	312	9371
MNPNSGKTEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGGLDF
DYWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SQRIGNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQSYSTPLTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYIHWVRQAPGQGLEWMGWMN	313	9372
PNTGDTGSAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDPAVTPDAF
DIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SQSISTYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYRTVTFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYAISWVRQAPGQGLEWMGIIDPS	314	9373
GGGTSYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAGSLYYYGMDVW
GQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLSCRASQSV
GSYLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVY
YCQQYDSSSQTFGQGTKVEIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFGSSAISWVRQAPGQGLEWMGGIIPIF	315	9374
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKEDDILPPRAFDIW
GQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLSCRASRSV
STYLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYY
CQQYDGSPYTFGQGTKLEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISG	316	9375
GGGVTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYSSGWLDAF
DIWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSS
QSLLHSNGYNYLDWYLQKPGQSPQLLIYDASNLETGVPDRFSGSGSGTDFTLKISR
VEAEDVGVYYCMQALQTPPAFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWISG	317	9376
YNGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSDVSPDAFDI
WGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLSSSYNKNFLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSAPPTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTQNIYAITWVRQAPGQGLEWVGWVN	318	9377
PNSGNTGYSQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATPTSSSDDAF
DIWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSS
QSVLSSSYNKNFLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTIS
SLQAEDVAVYYCQQYYSDPITFGQGTKLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	319	9378
NSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARASRGDDAFDI
WGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLSSSYNKNYLAWYQQKPGQPPKLLIYWASARESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSIPIAFGQGTRLEIK
QVQLVQSGAEVKKPGASVKVSCKASGIPFTSDDINWVRQAPGQGLEWMGIINPS	320	9379
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERYEGGYSSGP
GNYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGE
RATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWASTRDSGVPDRFSGSGS
GTDFTLTISSLQAEDVAVYYCQQYYSIPYTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGWM	321	9380
NPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDDYGDY
PVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSS
QSVLSTSYNKNYLAWYQQKPGQPPKLLIYWASTRASGVPDRFSGSGSGTDFTLTIS
SLQAEDVAVYYCQQYYTTPPTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGDTFSDHAINWVRQAPGQGLEWMGWM	322	9381
NPKIGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCVYDSSGYDAF
DIWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSS
QSVLSTSYNRNFLAWYQQKPGQPPKLLIYWASTRQSGVPDRFSGSGSGTDFTLTIS
SLQAEDVAVYYCQQYYSTPYTFGQGTKLEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGRINP	323	9382
GTGGTDYAHKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARETPSDYYDSS
GYYYNDAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGE
RATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSG
SGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWVGIIIPSG	324	9383
GTNYAQTFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDLGTTFDIWGQGTT
VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLN
WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQS
YSTPTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTAYYLHWVRQAPGQGLEWIGWINP	325	9384
DNDNAYYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDIAVAALAYG
MDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
QASQDISNYLNWYQQKPGKAPKLLIYGASTLQSGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQEADSFPLTFGGGTKVEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAVISYD	326	9385
GSDQYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQSLYYYYGMDV
WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
GIRNDLGWYQQKPGKAPKLLIYDASSLHSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQAYSFPWTFGQGTKLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYVHWVRQAPGQGLEWVGWIST	327	9386
FTGNTDYAQNFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDAPLAAAGTDY
YYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTI
TCRASQGISNYLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQSYNTPFTFGQGTRLEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAFISDD	328	9387
GITKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDDSSGYGGMDV
WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
SINRWLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSYNTPLTFGGGTKVEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYD	329	9388
GGDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASGSLVLGYYYMD
VWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSINTWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQANSFPFTFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYIHWVRQAPGQGLEWMGWIN	330	9389
PNTGGTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATGGGGSYYD
AFDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
RASQSIRTWLAWYQQKPGKAPKLLIYDASSLETGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQQLNSYPLTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRINP	331	9390
NSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIGEGYSMD
VWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSIRTYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYSAPLTFGGGTKLEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNHYTSWVRQAPGKGLEWVAVISYDG	332	9391
SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREEKYSSSWYVGV
DAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
RASQSISTYLNWYQQKPGKAPKLLIYAASSLHSGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQSYSTPLTFGGGTKVEIK
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSAMHWVRQAPGKGLEWISSISGSG	333	9392
DNAYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQEDYYYDSSGY
GMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
RASQSITTYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQSYSTPLTFGGGTKVEIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSHAISWVRQAPGQGLEWMGGIIPIF	334	9393
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKGDWGIVVVPAAI
GAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISC
RSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYAASSLQSGVPDRFSGSGSGTDFTLKI
SRVEAEDVGVYYCMQARQTPLTFGQGTRLEIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTAYYMHWVRQAPGQGLEWVGRISP	335	9394
VFGSTTYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDLGYYDSSGYRY
DAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISC
RSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYGASSLQSGVPDRFSGSGSGTDFTLK
ISRVEAEDVGVYYCMQTLQTPFTFGPGTKVDIK
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGGISP	336	9395
MFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKDGWYYGMDV
WGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQS
LLHSNGYNYLDWYLQKPGQSPQLLIYLGSDRASGVPDRFSGSGSGTDFTLKISRVE
AEDVGVYYCMQALQTPLTFGPGTKVDIK
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWINP	337	9396
NSGGTKYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGEAGNLDWYF
DLWGRGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSS
QTVFSTSYNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTIS
SLQAEDVAVYYCQQYYSTPLTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYGISWVRQAPGQGLEWMGWIN	338	9397
PNNGDTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDVWYFDL
WGRGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKTSQS
VFSTSYNRDYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSSPPTFGQGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGISWVRQAPGQGLEWMGWIST	339	9398
YDGKTNYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCALHLGGDWYFD
LWGRGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
SISSWLAWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSYSTPFTFGPGTKVDIK
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI	340	9399
NPNTGATYYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARQHGDYD
WYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTIT
CRASQSISSYLNWYQQKPGKAPKLLIYDASNLKTGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQQSYSFPTFGGGTKVEIK
QVQLVQSGAEVKKPGASVKVSCKASGDTFTTYYVHWVRQAPGQGLEWMGWIN	341	9400
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGRHWG
QGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLSCRASQSVSS
YLAWYQQKPGQAPRLLIYDTSSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYC
QQYYDTPYTFGQGTKLEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGRIIPM	342	9401
LGIANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCVREEVAGANWFDP
WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQS
VLYSSNNKNYLAWYQQKPGQPPKLLIYLASTREPGVPDRFSGSGSGTDFTLTISSLQ
AEDVAVYYCQQYYSTPPTFGGGTKLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGIINP	343	9402
SGGSTSYARKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGDYGSGEFD
YWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQ
SVLSSSYNKNYVAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSL
QAEDVAVYYCQQYYSTPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSSYMHWVRQAPGQGLEWMGWM	344	9403
NPRSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERDDYGD
YGWLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTI
TCQASQDISNYLNWYQQKPGKAPKLLIYAAASLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQTYSTPWTFGQGTRLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGIIN	345	9404
PSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLYDSSGYW
HYYYYMDVWGKGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDR
VTITCRASQDINTYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
SLQPEDFATYYCQQSSSFPLTFGQGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAFSWVRQAPGQGLEWMGWINP	346	9405
NSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARFSGYDYVDYW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDI
SNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQLYNFPYTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPN	347	9406
GGNTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVGEDFDLWG
QGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSIS
RYLAWYQQKPGKAPKLLIYGASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYY
CQQSYNTPLTFGQGTKLEIKR
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYYIHWVRQAPGQGLEWLGVINPA	348	9407
DGDTTYAQMFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDFDWLFAMDV
WGKGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQT
LSGWLAWYQQKPGKAPKLLIYGASTLQGGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQYYSYPPTFGQGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYALNWVRQAPGQGLEWMGRIN	349	9408
PNGGTTYYAKNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKHGDHGFYV
WGLWTKGTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCFASQ
DIINYLNWYQQKPGKAPKLLIYEASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQSYSTPLTFGQGTKVEIKR
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGMINP	350	9409
NVGSATYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDSGTSWFD
PWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSISSYLNWYQQKPGKAPKLLIYDVFNLGTGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYSSPFTFGQGTRLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINP	351	9410
SDGSTSYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDRGSNYYYG
MDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
QASQDISNYLNWYQQKPGKAPKLLIYMASNLESGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQTNSFPLTFGQGTKLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTAYYVHWVRQAPGQGLEWMGWM	352	9411
NPNSGTTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSSDYYGD
YRADAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDR
VTITCRASQSISSYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTIS
SLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGVISPS	353	9412
GDATLYAQSFQGRVTITADESTSTAYMELSSLRSEDTAVYYCVKGLDHWGQGTLV
TVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYN
YLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYY
CMQALQSPWTFGQGTKLEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFSFSDYGMHWVRQAPGKGLEWVSAIGGI	354	9413
GDSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARMNYGDSNYYYY
YGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATI
NCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD
FTLTISSLQAEDVAVYYCQQYYSSPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDISWVRQAPGQGLEWMGMISP	355	9414
SDGSTTYAPKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGAVGFDYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHS
NGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDV
GVYYCMQALQTPPSFGQGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINT	356	9415
YSGYTDYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTTDDFLSFGYWGQ
GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASESVSTW
LAWYQQKPGKAPKLLIYKASRLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
QSYKTPYTFGQGTKLEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGYMFTDYYIHWVRQAPGQGLEWMGGIIP	357	9416
YFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSISGSYVLDAFD
IWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQ
SVLYSSNNKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISS
LQAEDVAVYYCQQYFTTPLTFGQGTKLEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGYTFNSYGISWVRQAPGQGLEWMGGIIPIF	358	9417
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWGYGDYADDA
FDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCR
ASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQSYSTPYTFGQGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNNDINWVRQAPGQGLEWMGWIN	359	9418
PIYGSANYAQNFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAADWRGFDYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSVLS
SSYNKNYLAWYQQKPGQPPKLLIYWASTRASGVPDRFSGSGSGTDFTLTISSLQAE
DVAVYYCQQYYDTPLTFGQGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEYAIHWVRQAPGQGLEWMGRMN	360	9419
PHNGDTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGDYLGYPI
DCWGRGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSISSYLNWYQQKPGKAPKLLIYKASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQNDSIPITFGQGTRLEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYSMSWVRQAPGKGLEWVAAIWQ	361	9420
DGNVKFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGNSGYVFW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSIS
RWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCLQDYSYPLTFGQGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPGQGLEWMGWIN	362	9421
PNTGDTAYAQKIQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARTAEAVAGLP
AFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCK
TSQSVFSTSYNRDYLAWYQQKPGQPPKLLIYWASTRAAGVPDRFSGSGSGTDFTL
TISSLQAEDVAVYYCQQYYYTSTFGQGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGGTSNNYAIDWVRQAPGQGLEWMGGIIP	363	9422
LFGTTTYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVTLYGDYDYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSINR
YLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANSFPPTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYSLITHWMHWVRQAPGQGLEWMGMI	364	9423
NPSDGVTYYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREYYGEGFD
YWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QGISNYLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYSTPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	365	9424
GGSTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDTAMDG
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQS
IDSYLNWYQQKPGKAPKLLIYKASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQSYSAPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYLHWVRQAPGQGLEWMGIITPS	366	9425
GGSTTYAHKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGGLASFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDIS
TWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYY
CQQVNSDPYTFGQGTRLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMN	367	9426
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGGWAMT
DAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTIT
CQASQDISNYLNWYQQKPGKAPKLLIYAASTLESGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQGDSLPLTFGGGTKVEIKR*
EVQLVESGGGLVKPGGSLRLSCAASGFTFDDYGMSWVRQAPGKGLEWVSLIYSG	368	9427
GDTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTRKEYYYDSSGYLRLF
DYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSDSFPYTFGQGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGGIN	369	9428
PIFGTSNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDISGYDYYYYG
MDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLSCR
ASQSVSTYLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSE
DFAVYYCQQHDSYPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTLNNYAFSWVRQAPGQGLEWMGMID	370	9429
PSDGTIAYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSDYDFWSGL
GGYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTI
TCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQANSFPPTFGQGTRLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGTIDP	371	9430
NSGGTMFAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSAEWELGG
SFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCR
ASESISTYLNWYQQKPGKAPKLLIYKASNLESGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQTDSTFITFGQGTKVEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNHYTSWVRQAPGKGLEWVSSIGVN	372	9431
GDTYYLDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGLVFSGRGHWY
FDLWGRGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRA
SRNIHDYLNWYQQKPGKAPKLLIYAASTLQTGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQTYSTPPTFGPGTKVDIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGRINP	373	9432
NGGNTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYEDADFDG
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQS
NDSYLNWYQQKPGKAPKLLIYKASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQSYSSPLTFGQGTKVEIKR
QVQLVQSGAEVKKPGASVKVSCKASGYTFSDHHVHWVRQAPGQGLEWMGW	374	9433
MNPDSGNTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSTSGV
DYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QSISDFLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQSYSSPYTFGQGTKVEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAVISYD	375	9434
GHDQFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGEQQLEGFYYY
YGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTIT
CQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQANRFPLTFGQGTKLEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLEWVAVISYD	376	9435
GSKEYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASDYGDYGTYDYW
GQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDI
SNYLNWYQQKPGKAPKLLIYKASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQSYNFPATFGQGTRLEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLEWVSGISG	377	9436
GGDDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREPLAYCGGDC
PGGFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASIS
CRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL
KISRVEAEDVGVYYCMQGTHWPETFGQGTKVEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMDWVRQAPGKGLEWVSAIGTG	378	9437
GDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHEDTAIFLDYWG
QGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISS
YLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQSYSTPLTFGQGTKLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGMIS	379	9438
PSDGSTTYAPKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYDAWSYG
MDVWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC
RASQGISDYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQQSYILPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWM	380	9439
NPNSGNTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDGVTGTDY
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
DINDFLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSYSAPYTFGQGTKLEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFAFSSYVLHWVRQAPGKGLEWVSAISGAG	381	9440
DSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREPTTVTDDWYFD
LWGRGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
SISNWLAWYQQKPGKAPKLLIYAASKLESGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSYSSPWTFGQGTRLEIKR*
EVQLVESGGGLVKPGGSLRLSCAASGFAFSSHWMHWVRQAPGKGLEWVSAISG	382	9441
NGDNSYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDRAPEYFDLW
GRGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGID
SWLAWYQQKPGKAPKLLIYAASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYY
CQQAYSFPLTFGGGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	383	9442
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDYGDYGGG
MDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCR
ASQNIGTWLAWYQQKPGKAPKLLIYRASSLESGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQAYSFPWTFGQGTKLEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGW	384	9443
MNPNSGHTGYAEKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDTSPRY
GDGFFDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT
ITCRASQNINNWLAWYQQKPGKAPKLLIYKASTLQSGVPSRFSGSGSGTDFTLTISS
LQPEDFATYYCQQADSFPPTFGQGTKVEIKR*
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLEWVAVTSY	385	9444
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARESGFSAEYFQH
WGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQ
DISSYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQLNRYPITFGQGTKVEIKR*
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	386	9445
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARATGLYCSGSCFD
YWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRAS
QDISNYLAWYQQKPGKAPKLLIYAASILHSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQYDSSFITFGQGTRLEIKR*

TABLE 20
VH Sequences
Table 20-VH sequences

	Binder	SEQ ID
Sequence	Name	NO:

QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEIFPGS	1	257
GHTSFNEKFKGKATFTADTSSNTAYIQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTLSSYWIEWVKQRPGHGLEWIGEILPGS	2	258
GSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGATSYNQKFKG	3	259
KATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGEYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	4	260
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTSYNQKFKG	5	261
KATFTVDTSSSTAYMHFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	6	262
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGANGYNQKFK	7	263
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	8	264
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	9	265
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	10	266
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	11	267
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLAVSS
LVKTGASVKISCKASGYSFTGFYMHWVKQSHGKGLEWIGYISSYNGATGYNQKFK	12	268
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGATGYNQKFK	13	26
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	14	270
NSGTTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	15	271
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLQQPGAELIKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	16	272
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFVYWG
QGTLVTVSA
EVQLQQSGAELVKPGASVKLSCTPSGFNIKDTSLHWVKQGPEQGLEWIGRIDPAN	17	273
GNTKYDPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCARGPDDGYFYYYSMD
YWGQGTSVTVSS
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	18	274
TYTGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDMATYFCARKYYDYEFAYW
GQGTLVTVSA
QVQLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	19	275
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHEEANWAWFAY
WGQGTLVTVSA
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	20	276
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCASYYGSSRSYWYLDV
WGAGTTVTVSS
QVKLVESGGDLVKPGGSLKLSCATSGFTFSSYGMSWVRQTPDKRLEWVATISSGG	21	277
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEGTAMYYCARHNYSNWDWFAY
WGQGTLVTVSA
EVQLQQSGAELVKPGASVKLSCTPSGFNIKDTSLHWVKQGPEQGLEWIGRIDPAN	22	278
GNTKYDPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCARGPDDGYFYYYSMD
YWGQGTSVTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	23	27
GSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGLIDP	24	280
SDSETHYNQVFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDVYYRFAYWG
QGTLVTVSA
QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWINWVKQRPGQGLEWIGNIYPS	25	281
DSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRGNYIDYWGQGT
TLTVSS
QVQLKESGPGLVAPSQSLSIPCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAGG	26	282
TTNYNSALMSRLSISKDNSKSQVFLKMYSLQTDDTAMYYCARGDGYDDGYAMDY
WGQGTSVTVSS
QVQLQQSGAELVKPGASVKLSCKASGSTFTTYYIYWVKQRPGQGLEWIGEINPSN	27	283
GGTNFNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTSYYTHETYYYAMDY
WGQGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMQWVKQRPGQGLEWIGEIDP	28	284
SDSYTNYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARAEYGYGNYPWF
AYWGQGTLVTVSA
QVQLQQPGAELVKPGASVKVSCKASGYTFTSYWMHWVKQRPGQGLEWIGRIHP	29	285
SDSDTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAIPYYYGGWYFDV
WGTGTTVTVSS
EVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	30	286
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARLYDAHWDYFDYW
GQGTTLTVSS
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	31	287
NSGNTNYNEKFKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCAIYYDYDAYYFD
YWGQGTTLTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	32	288
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCANPYYGYDVGYW
GQGTTLTVSS
EVQLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	33	289
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRHDDSSYDWFAYW
GQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWMHWVKQRPGQGLEWIGMIH	34	290
PNSGTTNYNEKFKSKATLTVDKSSSTTYMQLISLTSEDSAVYYCARFGDGYHFDYW
GQGTTLTVSS
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	35	291
TNTGEPTYAEEFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARWYPYFDYWGQ
GTTLTVSS
QVQLQQSGAELAKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGYINP	36	292
SSGYTKYNQKFKDKATLTADKSSSTAYMQLSSLTYEDSAVYYCARSDGSSGNWYFD
VWGTGTTVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	37	293
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAMD
YWGQGTSVTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	38	294
GSTSYNEKFKDKATFTADTSSNTAFMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVRQAPGHGLEWIGEVLPG	39	295
SGSTSYNEKFKGRATFTADTSSNTAYMQLSSLRSEDSAVYYCARRAYGYDEGFDY
WGQGTTVTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVRQAPGHGLEWIGEILPGS	40	296
GRTSYIEKFKGRATFTADTSSNTAYMQLSSLRSEDSAVYYCARRGYGYDEGFDYWG
QGTTVTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEVLPG	41	297
SGSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	42	298
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	43	299
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	44	300
DSTSYNEKFKGKTTFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATAYTFSIYWIEWVKQRPGHGLEWIGEILPGS	45	301
GSTNYNEKVKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEIFPGS	46	302
GHTSFNEKFKGKATFTADTSSNTAYIQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKMSCKATGYTFSNYWIEWVKQRPGHGLEWIGEILP	47	303
GSGSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDY
WGQGSTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	48	304
GSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVQQRPGHGLEWIGEILPGS	49	305
GYTSYIEQFKGKATFTADTSSNTAYMQLGSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTLSSYWIEWVKQRPGHGLEWIGEILPGS	50	306
GSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKISCKGTGYTFSSYWIEWVKQRPGHGLEWIGEISPGS	51	307
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFGTYWIEWVKQRPGHGLEWIGEILPGS	52	308
GTPNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDAGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISFKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	53	309
GSTSCNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	54	310
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKMSCKATGYTFSNYWIEWVKQRPGHCLEWIGEILP	55	311
GSGSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDY
WGQGSTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHCLEWIGEILPGS	56	312
GSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGVTGYNQKFK	57	313
GKATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGDYFDYWGQGTTLTVSS
LVKTGASVKISCKASGYSFTGYYMHWVKQSHGKSLEWIGYISSYNGATSYNQKFKG	58	314
KATFTVDTSSSTAYMQFNSLTSEDSAVYYCARGRYGEYFDYWGQGTTLTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLSSYGVHWVRQSPGKALEWLGVIWRG	59	315
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTSYGVHWVRQSPGKGLEWLGVIWRG	60	316
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDSAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGPVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWRG	61	317
GSTDNNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTRYGVHWVRQSPGKGLEWLGVIWRG	62	318
GSTDHNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTTYGVHWVRQSPGKGLEWLGVIWRG	63	319
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	64	320
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	65	321
NSGTTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	66	322
GSTYYNEKFKGKATLTADKSSNTVYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	67	323
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	68	324
GSSYYNEKFRGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQKTGQGLEWIGEIYPGS	69	325
GSSYYNEKFKGKATLTADKSSNTAYIQLSSLTSEDSAVYFCARRGERGPWFAYWGQ
GTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	70	326
NSGSPNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFAYWG
QGTLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	71	327
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQG
TLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	72	328
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQG
TLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	73	329
GSNYYNEKFKGKAIMTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	74	330
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQG
TLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVRQAPGQGLEWIGEIYPG	75	331
SGSSYYNEKFKGRATLTADKSSNTAYMQLSSLRSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	76	332
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQG
TLVTVSS
QVQLKESGPGLVAPSQSLSITCTVSGFSLTNYGVHWVRQPPGKGLEWLGVVWAG	77	333
GITNYNWALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARGDGYDDGYAM
DYWGQGTSVTVSS
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVLWAG	78	334
GITNYNSALMSRLSIRKDNSKSQVFLKMYSLHTDDTAMYYCARGDGYDDGYAMD
YWGQGTSVTVSS
QVQLKESGPGLVAPSQSLSIPCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAGG	79	335
TTNYNSALMSRLSISKDNSKSQVFLKMYSLQTDDTAMYYCARGDGYDDGYAMDY
WGQGTSVTVSS
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	80	336
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSAMDY
WGQGTSVTVSS
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYIHWVKQRPEQGLEWIGWIDPEN	81	337
GDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSSMDYW
GQGTSVTVSS
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	82	338
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNVALLRYSSAMDY
WGQGTSVTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	83	339
GSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMQWVKQRPGQGLEWIGEIDP	84	340
SDSYTNYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARAEYGYGNYPWF
AYWGQGTLVTVSA
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	85	341
TYTGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDMATYFCARKYYDYEFAYW
GQGTLVTVSA
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	86	342
TGGTAYNQKFKVKAILTADKSSSTAYMELRSLTSEDSAVYYCTRLGDYDVMDYWG
QGTSVTVSS
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	87	343
NSGNTNYNEKFKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCAIYYDYDAYYF
DYWGQGTTLTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	88	344
GSNYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCAREEKIYFDYWGQGT
TLTVSS
EVQLQQSGTVLARPGASVKMSCKTSGYTFTSYWMHWIKQRPGQGLEWIGAIYP	89	345
GNSDTTYNQKFKGKAKLTAVTSASTAYMELSSLTNEDSAVYYCTSLITTAYYFDYW
GQGTTLTVSS
QVQLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	90	346
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHEEANWAWFAY
WGQGTLVTVSA
QVQLQQSGPQLVSPGASVKISCKASGYSFTNYWMHWVKQRPGQGLEWIGMIDP	91	347
SDSETRLNQQFKDKATLTVDESSSTAYMQLSSPTSEDSAVYYCAIPYYAMDYWGQ
GTSVTVSS
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	92	348
NSGNTNYNEKNKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCATYYGNYVWYFDV
WGAGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	93	349
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCASYGSSYWYFDVW
GTGTTVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	94	350
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCASYYGSSRSYWYLDV
WGAGTTVTVSS
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	95	351
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARQNDSSWAWFAY
WGQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	96	352
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCALPYSNYGWYFDV
WGTGTTVTVSS
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	97	353
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSYWYFDV
WGTGTTVTVSS
EVQLQQSGAELVKPGASVKLSCTASGFNIKDYYMHWVKQRTEQGLEWIGRIDPE	98	354
DGETKYAPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCAAYGNSAWFAYWG
QGTLVTVSA
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVRQAPGKGLEWMGWIN	99	355
TNTGEPTYAEEFKGRFAFSLETSASTAYLQINNLRNEDTATYFCARWYPYFDYWGQ
GTTVTVSS
QVQLQQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWIN	100	356
TNTGEPTYAEEFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARWYPYFDYWGQ
GTTLTVSS
QVQLQQSGAELAKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGYINP	101	357
SSGYTKYNQKFKDKATLTADKSSSTAYMQLSSLTYEDSAVYYCARSDGSSGNWYFD
VWGTGTTVTVSS
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAGG	102	358
STNYNSALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCAREGGYTGYFDVWG
AGTTVTVSS
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	103	359
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAYSNYVPYYAMDY
WGQGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	104	360
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAMD
YWGQGTSVTVSS
EVQLQQSGAELVRPGALVKLSCKASGFNIKDYFMHWVKQRPEQCLEWIGWIDPE	105	361
TDNTIYDPKFQGKASITADTSSNTAYLQLSSLTSEDTAVYYCARSGNMGFTYWGQ
GTLVTVSA
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKCLEWVATISSGG	106	362
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCASQGGSSWGAMDY
WGQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKCLEWLGVIWSGG	107	363
STDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARKGYGYDWYFDVWG
TGTTVTVSS
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQCLEWIGEIDP	108	364
SDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSSYYYYAMDYW
GQGTSVTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	109	365
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISFKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	110	366
GSTNYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	111	367
DSTSYNEKFKGKTTFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATAYTFSIYWIEWVKQRPGHGLEWIGEILPGS	112	368
GSTNYNEKVKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDGGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	113	369
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	114	370
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKMSCKATGYTFSNYWIEWVKQRPGHGLEWIGEILP	115	371
GSGSTSYNEKFKGKATFTADTSSSTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDY
WGQGSTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVQQRPGHGLEWIGEILPGS	116	372
GYTSYIEQFKGKATFTADTSSNTAYMQLGSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	117	373
GSTSYNEKFKDKATFTADTSSNTAFMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEVLPG	118	374
SGSTSYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKGTGYTFSSYWIEWVKQRPGHGLEWIGEISPGS	119	375
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFGTYWIEWVKQRPGHGLEWIGEILPGS	120	376
GTPNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRAYGYDAGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISFKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	121	377
GSTSCNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	122	378
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	123	379
GRTSYIEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYWG
QGTTLTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLSSYGVHWVRQSPGKALEWLGVIWRG	124	380
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTSYGVHWVRQSPGKGLEWLGVIWRG	125	381
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDSAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGPVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWRG	126	382
GSTDNNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTRYGVHWVRQSPGKGLEWLGVIWRG	127	383
GSTDHNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTTYGVHWVRQSPGKGLEWLGVIWRG	128	384
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSVTSYGVHWVRQSPGKGLEWLGVIWRG	129	385
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTRYGVHWVRQSPGKGLEWLGVIWRG	130	386
GSTDHNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKNLYGHYVMDYW
GQGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	131	387
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	132	388
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTTYWMHWVKQRPGQGLEWIGMIH	133	389
PNSDNTNYNEKFKSKATLTVDKSSSTAYIQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	134	390
NSGNTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARWGDGYSFAYW
GQGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	135	391
GSTYYNEKFKGKATLTADKSSNTVYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	136	392
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQRTGQGLEWIGEIYPGS	137	393
GSSYYNEKFRGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLKQSGPELVKPGASVKMSCKASGYTFTDYVINWVKQKTGQGLEWIGEIYPGS	138	394
GSSYYNEKFKGKATLTADKSSNTAYIQLSSLTSEDSAVYFCARRGERGPWFAYWGQ
GTLVTVSA
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	139	395
PSDSETHYNQMFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDGYYRFAY
WGQGTLVTVSA
QVQLQQPGAELVRPGASVRLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	140	396
PSDSETHFNQMFKDKATLTVDKSSSTAYMQVSSLTSEDSAVYYCATYDIYYRFAYW
GQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	141	397
NSDSTNYNEKFKSKATLTVDKSSSTAYMHLSSLTSEDSAVYYCARPGGYGFADWG
QGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTTYWMHWVKQRPGQGLEWIGMIH	142	398
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFTYWG
QGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	143	399
NSGSPNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARPGGYGFAYWG
QGTLVTVSA
QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWINWVKQRPGQGLEWIGNIYPS	144	400
DSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRGNYIDYWGQGT
TLTVSS
QVQLQQPGAELVRPGASVKLSCKASGYTFTDYWINWVKQRPGQGLEWIGNIYPS	145	401
DSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRGNYIDYWGQGT
TLTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	146	402
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQG
TLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	147	403
GSNYYNEKFKGKAIMTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQ
GTLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	148	404
GSSYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARPGDLGFAYWGQG
TLVTVSA
QVQLKESGPGLVAPSQSLSITCTVSGFSLTNYGVHWVRQPPGKGLEWLGVVWAG	149	405
GITNYNWALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARGDGYDDGYAM
DYWGQGTSVTVSS
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVLWAG	150	406
GITNYNSALMSRLSIRKDNSKSQVFLKMYSLHTDDTAMYYCARGDGYDDGYAMD
YWGQGTSVTVSS
QVQLQQSGPQLVSPGASVKISCKASGYSFTSYWMYWVKQRPGQGLEWIGMIDP	151	407
SDSETRLNQKFKDRATLTVDKSSSTAYMQLSSPTSEDSAVYYCARTRNYWGQGTTL
TVSS
QVQLQQSGPQLVSPGASVKISCKASGYSFTSYWMYWVKQRPGQGLEWIGMIDP	152	408
SDSETRLNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCARTRNYWGQGTTL
TVSS
QVQLQQSGPQLVSPGASVKISCKASGYSFTSYWMYWVKQRPGQGLEWIGMIDP	153	409
SDSETRLNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCARTRNYWGQGTSL
TVSS
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	154	410
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSAMDY
WGQGTSVTVSS
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYIHWVKQRPEQGLEWIGWIDPEN	155	411
GDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNAPLLRYSSSMDYW
GQGTSVTVSS
EVQLQQSGAELVRSGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGWIDPE	156	412
NGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCNVALLRYSSAMDY
WGQGTSVTVSS
QVQLQQSGAELVKPGASVKLSCKASGYTFSNYYVYWVKQRPGQGLEWIGEINPS	157	413
NGDTNFNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYFCTSYYTHEAYYYAMD
CWGQGTSVTVSS
QVQLQQSGAELVRPGASVKLSCTASGFNIKDYYMHWVKQRPEQGLEWIGRIDPE	158	414
DGDTEYAPKFQGKATMTADTSSNTAYLQLSSLTSEDTAVYYCTPYSIYDAMDYWG
QGTSVTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	159	415
GSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGERGPWFAYWG
QGTLVTVSA
QVQLQQSGAELVRPGVSVKISCKGSGYSFTDYGMHWVKQSHAKSLEWIGVISTYY	160	416
GDASYNQKFKGKATMTVDKSSSTAYMELARLTSEDSAIYYCARQMDYDYTYYYA
MDYWGQGTSVTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWNGEIYPG	161	417
SGSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARMDGPWFAYWG
QGTLVTVSA
QVTLKVSGPGILQPSQTLGLACTFSGISLSTSGMGLSWLRQPSGKALEWLASIWNN	162	418
DNYYNPSLKSRLTISKETSNNQVFLKLTSVDTADSTTYYCAWRPYYRYDSFAYWGQ
GTLVTVSA
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	163	419
TGGTAYNQKFKVKAILTADKSSSTAYMELRSLTSEDSAVYYCTRLGDYDVMDYWG
QGTSVTVSS
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEIDP	164	420
SDSYTNYNQKFKGKSTLTVDKSSSTAYMQLSSLTSEDSAVYYCARAGRYGSSFDYW
GQGTTLTVSS
QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPSGKGLEWLAHIYWD	165	421
DDKRYNPSLKSRLTISKDTSRNQGFLKITSVDTADTATYYCAGRPDDYDGAWFPY
WGQGTLVTVSA
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	166	422
GSNYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCAREEKIYFDYWGQGT
TLTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	167	423
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARYDGYWFDYWG
QGTTLTVSS
EVQLQQSGTVLARPGASVKMSCKTSGYTFTSYWMHWIKQRPGQGLEWIGAIYP	168	424
GNSDTTYNQKFKGKAKLTAVTSASTAYMELSSLTNEDSAVYYCTSLITTAYYFDYW
GQGTTLTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	169	425
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAPETGDYGSSYVW
YFDVWGTGTTVTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	170	426
GSTYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARGKVTRFAYWGQG
TLVTVSA
EVQLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISDGG	171	427
SYTYYPDNVKGRFTISRDNAKNNLYLQMSHLKSEDTAMYYCARDQDSNWEYFDY
WGQGTSLTVSS
QIQLVQSGPELKKPGETVKISCKASGYTFTDYSMHWVRQAPGKGLKWMAWINTE	172	428
TGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARESWDRAMDYWG
QGTSVTVSS
QVQLQQSGPQLVSPGASVKISCKASGYSFTNYWMHWVKQRPGQGLEWIGMIDP	173	429
SDSETRLNQQFKDKATLTVDESSSTAYMQLSSPTSEDSAVYYCAIPYYAMDYWGQ
GTSVTVSS
QVQLQQPGSVLVRPGASVKLSCKASGYTFTSSWMHWAKQRPGQGLEWIGEIHP	174	430
NSGNTNYNEKNKGKATLTVDTSSSTAYVDLSSLTSEDSAVYYCATYYGNYVWYFDV
WGAGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	175	431
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCASYGSSYWYFDVW
GTGTTVTVSS
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGALYS	176	432
GNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSHLWY
FDVWGAGTTVTVSS
QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPSGKGLEWLAHIYWD	177	433
DDKRYNPSLKSRLTISKDTSRNQVFLKITSVDTADTATYYCARRAHYDYGWYFDVW
GAGTTVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	178	434
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAGYDYDWYFDVW
GTGTTVTVSS
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	179	435
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARHEDSNYHYFDYW
GQGTTLTVFS
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	180	436
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARQNDSSWAWFAY
WGQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	181	437
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCALPYSNYGWYFDV
WGTGTTVTVSS
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	182	438
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSYWYFDV
WGTGTTVTVSS
EVQLQQSGAELVKPGASVKLSCTASGFNIKDYYMHWVKQRTEQGLEWIGRIDPE	183	439
DGETKYAPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCAAYGNSAWFAYWG
QGTLVTVSA
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAGG	184	440
STNYNSALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCAREGGYTGYFDVWG
AGTTVTVSS
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	185	441
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCAYSNYVPYYAMDY
WGQGTSVTVSS
QVQLQQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGEIYPGS	186	442
GSAYYNEKFKGKATLTADKSSNTAYMQLSSLTSEDSAVYFCARRGFDYWGQGTTL
TVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	187	443
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSGYGYYFD
YWGQGTTLTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	188	444
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSYGWYF
DVWGTGTTVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	189	445
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSYGWYF
DVWGTGTTVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	190	446
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCASDYYGSSYGWYF
DVWGTGTTVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	191	447
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYYGSSYGWYF
DVWGTGTTVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	192	448
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRDYYGSGYGWYF
DVWGTGTTVTVSS
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	193	449
PSDSETHYNQMFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDGYYRFAY
WGQGTLVTVSA
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPGQGLEWIGMID	194	450
PSDSETHFNQMFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCATYDVYYRFAY
WGQGTLVTVSA
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	195	451
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAMD
YWGQGTSVTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIHP	196	452
NSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARDYGNYDYAMD
YWGQGTSVTVSS
EVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	197	453
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASQLTGTWYYFDYW
GQGTTLTVSS
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	198	454
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASQLTGTWYYFDYW
GQGTTLTVSS
QVKLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	199	455
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASQLTGTWYYFDYW
GQGTTLTVSS
DVKLVESGGGLVKLGGSLKLSCAASGFTFSNYYMSWVRQTPEKRLELVAVINSNG	200	456
GSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTALYYCARQEGIGYAMDYWG
QGTSVTVSS
EVQLQQSGPELVKPGASVKISCKTSGYTFTEYTMHWVKQSHGKSLEWIGGIYPNN	201	457
GGTSYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARGGWLLGYWGQG
TTLTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	202	458
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARDGGIRGAMDYWG
QGTSVTVSS
QVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPGHGLEWIGEILPGS	203	45
GSTNYNEKFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARRGYGYDEGFDYW
GQGTTLTVSS
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	204	460
TGGTAYNQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRNYDYAMDYWG
QGTSVTVSS
DVKLVESGGGLVKLGGSLKLSCAASGFTFSSYYMSWVRQTPEKRLELVAVINSNGG	205	461
STFYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTALYYCARQEGIGYALDYWGQG
TSVTVSS
EVKLVESGGDLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVAAISSGGS	206	462
TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCAREREWGVYYGSSLDY
WGQGTTLTVSS
EVQLQQSGAELVKPGASVKLSCTASGFNIKDTYMHWVKQRPEQGLEWIGRIDPA	207	463
NGNTKYDPKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCARSDGNYDWGQGT
LVTVSA
DVKLVESGGGLVKLGGSLKLSCAASGFTFSNYYMSWVRQTPEKRLELVAVINSNG	208	464
GSTYYPDTVKGRFTISRDNAKNILYLQMSSLKSEDTALYYCARQEGIGYGMDYWG
QGTSVTVSS
EVQLVESGGGLVQPKGSLKLSCAASGFTFNTYVMNWVRQAPGKGLEWVARIRSK	209	465
SDNYATYYADSVKDIFTISRDDSQSMLYLQMNNLKTEDTAMYYCVRHDGVVGFD
VWGAGTTVTVSS
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYD	210	466
GSNNYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCARGGGRGWGQGTLVT
VSA
QIQLVQSGPELKKPGETVKISCKASGYTFTDYSMHWVKQAPGKGLKWMGWINTE	211	467
TGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARDYYDYYYAMDYW
GQGTSVTVSS
QIQLVQSGPELKKPGETVKISCKASGYTFTDYSMHWVKQAPGKGLKWMGWINTE	212	468
TGEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARESWDRAMDYWG
QGTSVTVSS
QVQLQQPGAELVRPGASVKLSCKASGYTFTNYWMNWVKQRPEQGLEWIGRIDP	213	469
YDSETHYNQKFKDKAILTVDKSSSTAYMQLSSLTSEDSAVYYCARIYSDYDGAWFAY
WGQGTLVTVSA
EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMDWVKQSHGESFEWIGRVNP	214	470
YNGGTSYNQKFKGKATLTVDKSSSTAYMELNSLTSEDSAVYYCARGTVGFAYWGQ
GTLVTVSA
EVKLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVASISSGGS	215	471
TYYPDSVKGRFTISRDNARNILSLQMSSLRSEDTAMYYCAREREWGVFYGSSLDY
WGQGTTLTVSS
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWIRQTPEKRLEWVATISSGGS	216	472
YTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHDDSSYGYFDYWG
QGTTLTVSS
EVKLVESGGGLVKPGGSLKLSCAASGFTFSNYAMSWVRQTPEKRLEWVASISSGG	217	473
TTYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCARTMPDVWGAGTTVT
VSS
QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWAGG	218	474
STNYNSALMSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARDTDGYYWAMDY
WGQGTSVTVSS
DVQLQESGPGLVKPSQSLSLTCTVTGYSITSDHAWNWIRQFPGNKLEWMGYISYS	219	475
GSTTYNPSLKSRISITRDTSKNQFFLQLNSVTTEDTATYYCARKWGDYWGQGTSVT
VSS
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	220	476
TGGTAYNQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRNYDYALDYWGQ
GTSVTVSS
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYD	221	477
GSNDYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCARGGGRGWGQGTLVT
VSA
DVKLVESGGGLVKLGGSLKLSCAASGFTFSNYYMSWVRQTPEKRLELVAVINSNG	222	478
GSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTALYYCARQEEIGYAMDYWG
QGTSVTVSS
EVQLQQSGAELVRPGALVKLSCKASGFNIKDYFMHWVKQRPEQGLEWIGWIDPE	223	479
TDNTIYDPKFQGKASITADTSSNTAYLQLSSLTSEDTAVYYCARSGNMGFTYWGQ
GTLVTVSA
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	224	480
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCASQGGSSWGAMDY
WGQGTSVTVSS
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISNGG	225	481
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARHEITTRFAYWGQG
TLVTVSA
VQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYMSYD	226	482
GSNNYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCAREAGYFDYWGQGTT
LTVSS
EVQLVESGGGLVQPKGSLKLSCAASGFSFNTYAMNWVRQAPGKGLEWVARIRSK	227	483
SNNYATYYADSVKDRFTISRDDSESMLYLQMNNLKTEDTAMYYCVRQYGYDFDY
WGQGTTLTVSS
EVQLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLEWVATISSGG	228	484
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARHKGVNWDYFDY
WGQGTTLTVSS
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	229	485
TGGTAYNQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRGDGNYDSWYFD
VWGAGTTVTVSS
EVMLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	230	486
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARLPVTTVVFDYWG
QGTTLTVSS
EVQLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGG	231	487
SYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARRPVVVPFDYWGQ
GTTLTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	232	488
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARGWDADYFDYWGQ
GTTLTVSS
QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWMHWVKQRPGQGLEWIGMIH	233	489
PNSGSTNYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRYDYDDYWGQ
GTTLTVSS
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGDINPN	234	490
NGGTSYNQKFKGKATLTVDKSSSTAYMDLRSLTSEDSAVYYCARSELGLYAMDYW
GQGTSVTVSS
QVQLQQSGAELMKPGASVKLSCKATGYTFTGYWIEWVKQRPGHGLEWIGEILPG	235	491
SGSTNYNEKFKGKATFTADTSSNTAYMQLSSLTTEDSAIYYCARGRIHYFDYWGQG
TTLTVSS
QVQLQQSGAELMKPGASVKLSCKATGYTFTGYWIEWVKQRPGHGLEWIGEILPG	236	492
SGSTNYNEKFKGKATFTADTSSNTAYMQLSSLTTEDSAIYYCARGRIHYFDYWGQG
TTLTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	237	493
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARKGYGYDWYFDVW
GTGTTVTVSS
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEIDP	238	494
SDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSSYYYYAMDYW
GQGTSVTVSS
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYD	239	495
GSNNYNPSLKNRISITRDTSKNQFFLKLNSVTTEDTATYYCARGGGRDWGQGTTLT
VSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	240	496
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARGGDYDSYAMDYW
GQGTSVTVSS
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYWITWVKQRPGQGLEWIGDIYPG	241	497
SGSTNYNEKFKSKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARESVYDGYSWYFD
VWGTGTTVTVSS
EFQLQQSGPELVKPGASVKISCKASGYSFTDYNMNWVKQSNGKSLEWIGVINPNY	242	498
GTTSYNQKFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCASTYDYDDWYFDV
WGTGTTVTVSS
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEIDP	243	499
SDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSGNYLYAMDY
WGQGTSVTVSS
EFQLQQSGPELVKPGASVKISCKASGYSFTDYNMNWVKQSNGKSLEWIGVINPNY	244	500
GTTSYNQKFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCAREGTSWYFDVWG
TGTTVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWRG	245	501
GSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKKGDGYDWYFDV
WGTGTTVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	246	502
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCAREGNYGSSYDAMDY
WGQGTSVTVSS
QVQLQQPGAELVMPGASVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGEIDP	247	503
SDSYTNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARSSNYPYAMDY
WGQGTSVTVSS
EVQLQQSVAELVRPGASVKLSCTASGFNIKNTYMHWVKQRPEQGLEWIGRIDPA	248	504
NGNTKYAPKFQGKATITADTSSNTAYLQLSSLTSEDTAIYYCAYYSGLYWGQGTLVT
VSA
QVQLQQPGAELVRPGSSVKLSCKASGYTFTSYWMHWVKQRPIQGLEWIGNIDPS	249	505
DSETHYNQKFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCARRGQIYYGYSWFA
YWGQGTLVTVSA
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGDINPN	250	506
NGGTSYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARSTVVADWYFDV
WGTGTTVTVSS
QVQLQQSGAELARPGASVKLSCKASGYTFTSYGISWVKQRTGQGLEWIGEIYPRS	251	507
GNTYYNEKFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCARSGSSYGYFDVWGT
GTTVTVSS
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLGVIWSG	252	508
GSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARKGGYDAYAMDYW
GQGTSVTVSS
EFQLQQSGPELVKPGASVKISCKASGYSFTDYNMNWVKQSNGKSLEWIGVINPNY	253	509
GTTSYNQKFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCAREGFITTVVAVDY
WGQGTTLTVSS
QVQLQQSGAELVRPGASVTLSCKASGYTFTDYEMHWVKQTPVHGLEWIGAIDPE	254	510
TGGTAYNQKFKGKAILTADKSSSTAYMELRSLTSEDSAVYYCTREGNYDAMDYWG
QGTSVTVSS
QVQLQQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDP	255	511
SDSYTNYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYYCARWDYYGVDYWG
QGTTLTVSS
EVQLVESGGGLVQSGGSLRLSCAASGFTFSGYWMYWVRQAPGKGLEWVSAISPG	256	256
GGSTYYPDSVKGRFTISRDNAKNTLYLQMNSLEPEDTALYYCASSLTATHTYEYDY
WGQGTQVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQCLEWMGWINP	257	9447
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGSYSD
WGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQCLEWMGGIIPLS	258	9448
GAPNYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGALYNWNDGWF
DPWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYSLITHWMHWVRQAPGQCLEWMGMIN	259	9449
PSDGVTYYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREYYGEGFDY
WGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSDHHVHWVRQAPGQGLEWMGGIIPI	260	9450
FGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSSWYLHFQHW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYGIAWVRQAPGQGLEWMGISYPS	261	9451
DGSTSSAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRLGDLDYWG
QGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYVHWVRQAPGQGLEWVGWIST	262	9452
FTGNTDYAQNFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDAPLAAAGTDY
YYGMDVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYALSWVRQAPGQGLEWMGIINPS	263	9453
GGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDPGMDVW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	264	9454
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGSYSD
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYALSWVRQAPGQGLEWMGIINPS	265	9455
GGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDPGMDVW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIIDPS	266	9456
GGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDMGMDV
WGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAFSWVRQAPGQGLEWMGIINP	267	9457
SGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVGDRGMDV
WGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGSTFSGYYMHWVRQAPGQGLEWMGWID	268	9458
PNGGGTQYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDIVHDGTEY
FQHWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINP	269	9459
SGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDIVHDGTEYFQ
HWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	270	9460
GGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGRDHDAFDI
WGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGFTFTDYGISWVRQAPGQGLEWMGIINPS	271	9461
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGRSHDAFDIW
GQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWM	272	9462
NPHSGDTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARWVGTTEY
YYYYYMDVWGKGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYLHWVRQAPGQGLEWMGIIDPS	273	9463
GGSTSIAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATTAYYDFWSGYS
MDVWGKGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSHYMHWVRQAPGQGLEWMGIIDP	274	9464
SGGSTSYAQEFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDMDNWNTGY
YYYMDVWGKGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAINWVRQAPGQGLEWMGWVN	275	9465
PNSGDTAYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQRGGDA
WDVWGKGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIITPS	276	9466
GGSTTYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDTAGHFDIWGQ
GTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFRNDVINWVRQAPGQGLEWIGWMN	277	9467
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNPDLDGM
DVWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAINWVRQAPGQGLEWLGWISAY	278	9468
NGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLVGHFDYWG
QGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	279	9469
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGSYSD
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGNTLSSHAISWVRQAPGQGLEWMGIINPS	280	9470
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQGSSGTFDYW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYAISWVRQAPGQGLEWMGWINP	281	9471
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSTDVIDYW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYIFTSYDINWVRQAPGQGLEWMGWINP	282	9472
NSGDTKYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGGTVTPTEE
YYYYGMDVWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWISV	283	9473
YNGNTNYAQNLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASLDDLDYWGQ
GTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGHTFTSYYIHWVRQAPGQGLEWMGWINP	284	9474
NNGGTHYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDMVRDSAEY
FQHWGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFITSYIHWVRQAPGQGLEWMGMINPS	285	9475
GGTTTYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDSSGYPIDYWGQ
GTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGGIIPL	286	9476
SGAPNYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGALYNWNDGW
FDPWGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTVGSWYMSWVRQAPGKGLEWVAGIWY	287	9477
EGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLGTASLPYFDY
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWVGWIN	288	9478
PNRGDTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARESGDGFDP
WGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTNYYIHWVRQAPGQGLEWMGWMN	289	9479
PNSGNTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWPNWFDP
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYSFTDNYIHWVRQAPGQGLEWMGWIRS	290	9480
DNGETSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREVQLVGFDY
WGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSDHHVHWVRQAPGQGLEWMGGIIPI	291	9481
FGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSSWYLHFQHW
GQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIYWVRQAPGQGLEWMGGIIPIF	292	9482
GTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKGVDRYNWNDAFD
YWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWIH	293	9483
SNSGGTHSAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARESSGYDSSLD
YWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYGISWVRQAPGQGLEWVGWINP	294	9484
NSGDTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTDPRLDSSDPG
YWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFGNYGINWVRQAPGQGLEWMGWIS	295	9485
AYNGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGMDVWG
QGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYGIAWVRQAPGQGLEWMGISYPS	296	9486
DGSTSSAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRLGDLDYWG
QGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMN	297	9487
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSIVGGYPF
DYWGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGTITPIF	298	9488
GTTDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYSSSWHDDAFD
IWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGIIDPS	299	9489
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDYGLDSW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWM	300	9490
NPNSGDTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATGGSDSSGY
YYEGYFQHWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWLGYMSP	301	9491
NSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDKGGYYDSSG
YYWYWGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFSLSSYEMHWVRQAPGKGLEWVSAISSNG	302	9492
GSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGDGDGYNPDFD
YWGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWIDP	303	9493
TSGATDTAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKDPIVATEVDYW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMS	304	9494
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGAFDIW
GQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGVTISNYAISWVRQAPGQGLEWMGWMN	305	9495
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGLLDAFDI
WGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSRYGITWVRQAPGQGLEWMGWM	306	9496
NPYDGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGRHHDA
FDIWGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	307	9497
GDGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDISNDAFDIWG
QGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYILTGHYMHWVRQAPGQGLEWMGWIS	308	9498
AYNGDTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGSSWDDAF
DIWGQGTMVTVSS
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNHYTSWVRQAPGKGLEWVSAIGAG	309	9499
GGTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCAREGWNDDVFDIW
GQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWVGIINPSA	310	9500
GTTYYAERFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGNFGAFDIWGQ
GTMVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTTYAITWVRQAPGQGLEWMGEIIPIF	311	9501
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDKSGWNYGSGSY
NDAFDIWGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYAFTGYYMHWVRQAPGQGLEWMGW	312	9502
MNPNSGKTEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGGLDF
DYWGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYIHWVRQAPGQGLEWMGWMN	313	9503
PNTGDTGSAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDPAVTPDAF
DIWGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYAISWVRQAPGQGLEWMGIIDPS	314	9504
GGGTSYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAGSLYYYGMDVW
GQGTMVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFGSSAISWVRQAPGQGLEWMGGIIPIF	315	9505
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKEDDILPPRAFDIW
GQGTMVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISGG	316	9506
GGVTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYSSGWLDAFDI
WGQGTMVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWISG	317	9507
YNGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASSDVSPDAFDI
WGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTQNIYAITWVRQAPGQGLEWVGWVN	318	9508
PNSGNTGYSQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATPTSSSDDAF
DIWGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	319	9509
NSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARASRGDDAFDI
WGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGIPFTSDDINWVRQAPGQGLEWMGIINPS	320	9510
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERYEGGYSSGP
GNYYYGMDVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGWM	321	9511
NPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDDYGDY
PVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGDTFSDHAINWVRQAPGQGLEWMGWM	322	9512
NPKIGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCVYDSSGYDAF
DIWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGRINP	323	9513
GTGGTDYAHKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARETPSDYYDSS
GYYYNDAFDIWGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWVGIIIPSG	324	9514
GTNYAQTFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDLGTTFDIWGQGTT
VTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTAYYLHWVRQAPGQGLEWIGWINP	325	9515
DNDNAYYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDIAVAALAYG
MDVWGQGTTVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAVISYD	326	9516
GSDQYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQSLYYYYGMDV
WGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYVHWVRQAPGQGLEWVGWIST	327	9517
FTGNTDYAQNFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDAPLAAAGTDY
YYGMDVWGQGTTVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAFISDD	328	9518
GITKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDDSSGYGGMDV
WGQGTTVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYD	329	9519
GGDKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASGSLVLGYYYMD
VWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYIHWVRQAPGQGLEWMGWINP	330	9520
NTGGTDYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATGGGGSYYDAF
DVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGRINP	331	9521
NSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIGEGYSMD
VWGQGTTVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNHYTSWVRQAPGKGLEWVAVISYDG	332	9522
SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREEKYSSSWYVGVD
AFDIWGQGTTVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSAMHWVRQAPGKGLEWISSISGSG	333	9523
DNAYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQEDYYYDSSGY
GMDVWGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSHAISWVRQAPGQGLEWMGGIIPIF	334	9524
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKGDWGIVVVPAAIG
AFDIWGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTAYYMHWVRQAPGQGLEWVGRISP	335	9525
VFGSTTYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDLGYYDSSGYRY
DAFDIWGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGGISP	336	9526
MFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAKDGWYYGMDV
WGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWINP	337	9527
NSGGTKYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGEAGNLDWYF
DLWGRGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYGISWVRQAPGQGLEWMGWIN	338	9528
PNNGDTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDVWYFDL
WGRGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGISWVRQAPGQGLEWMGWIST	339	9529
YDGKTNYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCALHLGGDWYFDL
WGRGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI	340	9530
NPNTGATYYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARQHGDYDW
YFDLWGRGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGDTFTTYYVHWVRQAPGQGLEWMGWIN	341	9531
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGRHWGQ
GTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGRIIPM	342	9532
LGIANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCVREEVAGANWFDP
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGIINP	343	9533
SGGSTSYARKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGDYGSGEFDY
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSSYMHWVRQAPGQGLEWMGWM	344	9534
NPRSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERDDYGDY
GWLDYWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGIINP	345	9535
SGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLYDSSGYWH
YYYYMDVWGKGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAFSWVRQAPGQGLEWMGWINP	346	9536
NSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARFSGYDYVDYW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPN	347	9537
GGNTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVGEDFDLWG
QGTMVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYYIHWVRQAPGQGLEWLGVINPA	348	9538
DGDTTYAQMFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDFDWLFAMDV
WGKGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYALNWVRQAPGQGLEWMGRIN	349	9539
PNGGTTYYAKNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKHGDHGFYV
WGLWTKGTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGMINP	350	9540
NVGSATYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDSGTSWFDP
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINP	351	9541
SDGSTSYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDRGSNYYYG
MDVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTAYYVHWVRQAPGQGLEWMGWM	352	9542
NPNSGTTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSSDYYGD
YRADAFDIWGQGTMVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGVISPS	353	9543
GDATLYAQSFQGRVTITADESTSTAYMELSSLRSEDTAVYYCVKGLDHWGQGTLV
TVSS
EVQLLESGGGLVQPGGSLRLSCAASGFSFSDYGMHWVRQAPGKGLEWVSAIGGI	354	9544
GDSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARMNYGDSNYYYY
YGMDVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDISWVRQAPGQGLEWMGMISPS	355	9545
DGSTTYAPKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGAVGFDYWGQ
GTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINT	356	9546
YSGYTDYAHKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTTDDFLSFGYWGQ
GTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYMFTDYYIHWVRQAPGQGLEWMGGIIP	357	9547
YFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSISGSYVLDAFDI
WGQGTTVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFNSYGISWVRQAPGQGLEWMGGIIPIF	358	9548
GTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWGYGDYADDAF
DIWGQGTMVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNNDINWVRQAPGQGLEWMGWIN	359	9549
PIYGSANYAQNFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAADWRGFDYWG
QGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEYAIHWVRQAPGQGLEWMGRMN	360	9550
PHNGDTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGDYLGYPI
DCWGRGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYSMSWVRQAPGKGLEWVAAIWQ	361	9551
DGNVKFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGNSGYVFW
GQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPGQGLEWMGWIN	362	9552
PNTGDTAYAQKIQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARTAEAVAGLP
AFDYWGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGGTSNNYAIDWVRQAPGQGLEWMGGIIPL	363	9553
FGTTTYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVTLYGDYDYWGQ
GTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYSLITHWMHWVRQAPGQGLEWMGMI	364	9554
NPSDGVTYYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREYYGEGFD
YWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	365	9555
GGSTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLGDTAMDG
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYLHWVRQAPGQGLEWMGIITPS	366	9556
GGSTTYAHKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGGLASFDYWG
QGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMN	367	9557
PNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGGWAMT
DAFDIWGQGTMVTVSS
EVQLVESGGGLVKPGGSLRLSCAASGFTFDDYGMSWVRQAPGKGLEWVSLIYSG	368	9558
GDTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTRKEYYYDSSGYLRLF
DYWGQGTLVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGGIN	369	9559
PIFGTSNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDISGYDYYYYG
MDVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTLNNYAFSWVRQAPGQGLEWMGMID	370	9560
PSDGTIAYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSDYDFWSGL
GGYFDYWGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGTIDP	371	9561
NSGGTMFAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSAEWELGG
SFDYWGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNHYTSWVRQAPGKGLEWVSSIGVNG	372	9562
DTYYLDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGLVFSGRGHWYF
DLWGRGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAISWVRQAPGQGLEWMGRINP	373	9563
NGGNTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYEDADFDG
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFSDHHVHWVRQAPGQGLEWMGWM	374	9564
NPDSGNTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSTSGVDY
WGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAVISYD	375	9565
GHDQFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGEQQLEGFYYY
YGMDVWGQGTTVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLEWVAVISYD	376	9566
GSKEYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASDYGDYGTYDYW
GQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLEWVSGISGG	377	9567
GDDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREPLAYCGGDCP
GGFDYWGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMDWVRQAPGKGLEWVSAIGTG	378	9568
GDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHEDTAIFLDYWG
QGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGMIS	379	9569
PSDGSTTYAPKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYDAWSYG
MDVWGQGTMVTVSS
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWM	380	9570
NPNSGNTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDGVTGTDY
WGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFAFSSYVLHWVRQAPGKGLEWVSAISGAG	381	9571
DSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREPTTVTDDWYFDL
WGRGTLVTVSS
EVQLVESGGGLVKPGGSLRLSCAASGFAFSSHWMHWVRQAPGKGLEWVSAISG	382	9572
NGDNSYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDRAPEYFDLW
GRGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINP	383	9573
NSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDYGDYGGG
MDVWGQGTTVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWM	384	9574
NPNSGHTGYAEKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKDTSPRYGD
GFFDYWGQGTLVTVSS
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLEWVAVTSY	385	9575
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARESGFSAEYFQH
WGQGTLVTVSS
QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGIINPS	386	9576
GGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARATGLYCSGSCFD
YWGQGTLVTVSS
DLGKKLLEAARAGQDDEVRILMANGADVNAMDHFGFTPLHLAAKVGHLEIVEVLL	387	14114
KYGADVNADDMDGETPLHLAAAIGHLEIVEVLLKNGADVNAHDTWGFTPLHLAA
SYGHLEIVEVLRKYGADVNAQDKFGETTFDISIDNGNEDLAEILQKLN
EVQLVESGGGLVQAGGSLKLSCAASRSILDFNAMGWYRQAPGKQREWVTTIARA	388	14115
GATKYADSVKGRFSISRDNAKNTVYLQMSSLKPEDTATYYCNARVFDLPNDYWG
QGTQVTVSS
EVQLVESGGGLVQAGGSLRLSCAASGRTSASYSMGWFRQAPGKERE	389	14000
FVAAISWSGDETSYADSVKGRFTIARGNAKNTVYLQMNSLKSEDTA
IYYCAGDRWWRPAGLQWDYWGQGTQVTVSS
EVQLVESGGGLVQAGGSLKLSCAASRSILDFNAMGWYRQAPGKQRE	390	14001
WVTTIARAGATKYADSVKGRFSISRDNAKNTVYLQMSSLKPEDTAT
YYCNARVFDLPNDYWGQGTQVTVSS
EVQLVESGGGSVQPGGSLTLSCGTSGRTFNVMGWFRQAPGKEREFV	391	14002
AAVRWSSTGIYYTQYADSVKSRFTISRDNAKNTVYLEMNSLKPEDT
AVYYCAADTYNSNPARWDGYDFRGQGTQVTVSS

TABLE 21
VL Sequences
Table 21-VL sequences

	Binder	SEQ ID
Sequence	Name	NO:

DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	1	512
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	2	513
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVFAATYLADG	3	514
VPSRFSGSGSGTQYSLKINSLQSEDFGNYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	4	515
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQVLVYAATNLAD	5	516
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGSPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPRLLVYAATNLAD	6	517
GVPSRFSGSGSGTQYSLKITSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	7	518
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQVLVYAATNVAD	8	519
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASDNIYSNLAWYQQKQGKSPQLLVYAATNLAD	9	520
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPRLLVYAATNLAD	10	521
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	11	522
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVFAATYLADG	12	523
VPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	13	524
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGSPWTFGGGTKLEIK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWFQQKSGTSPKRWIYDTSKLASG	14	525
VPARFSGSGSGTSYSLTFSSMEAEDAATYYCQQWSSNPLYTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	15	526
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGGGTKLELK
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	16	527
VPSRFSGSGSGSDYSLTINNLESEDFADYYCLQFYEFPLTFGAGTKLELK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	17	528
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIVMTQSPSSLAMSVGQKVTMSCKSSQSLLNSSNQKNYLAWYQQKPGQSPKLLVY	18	529
FASTRESGVPDRFIGSGSGTDFTLTISSVQAEDLADYFCQQHYSTPLTFGAGTKLELK
QIVLTQSPAIMSASPGEKVTITCSASSSVSYMHWFQQKPGTSPKLWIYSTSNLASGV	19	530
PARFSGSGSGTSYSLTISRMEAEDAATYYCQQRSSFPYTFGGGTKLEIK
SIVMTQTPKFLLVSAGDRVTITCKASQSVSNDVAWYQQKPGQSPKLLIYYASNRYTG	20	531
VPDRFTGSGYGTDFTFTISTVQAEDLAVYFCQQDYTSLPTFGAGTKLEIK
DIQMTQSPSSLSASLGDTITITCHASQNINVWLSWYQQKPGNIPKLLIYKASNLHTG	21	532
VPSRFSGSGSGTGFTLTISSLQPEDIATYYCQQGQSYPLTFGGGTNLEIK
ETTVTQSPASLSMAIGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNSLRPG	22	533
VPSRFSSSGYGTDFVFTIENMLSEDVADYYCLQSDNLPLTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	23	534
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPSLLIHYTSTLQP	24	535
GIPSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDNLMYTFGGGTKLEIK
ENVLTQSPAIMSASLGEKVTMSCRASSSVNYMYWYQQKSDASPKLWIYYTSNLAP	25	536
GVPGRFSGSGSGNSYSLTISSMEGEDAATYYCQQFTSSHTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQPPKLLIKYASN	26	537
LESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWEIPLTFGAGTKLELK
ETTVTQSPASLSVATGEKVSIRCMTSIDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	27	538
VPSRFSSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPFTFGSGTKLEIK
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	28	539
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHWVFGGGTKLTVL
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNNR	29	540
APGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHLFGSGTKVTVL
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNNR	30	541
APGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHWVFGGGTKLTVL
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	31	542
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPYTFGGGTKLEIK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMYWYQQKPGSSPRLLIYDTSNLASGV	32	543
PVRFSGSGSGTSYSLTISRMEAEDAATYYCQQWSSYPLTFGAGTKLELK
ETTVTQSPASLSVATGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	33	544
VPSRFFSGGYGTDFVFTIENTLSEDVADYYCLQSDNMPLMFGAGTKLELK
QIVLTQSPAIMSASPGEKVTITCSASSSVSYMHWFQQRPGTSPKLWIYSTSNLASGV	34	545
PARFSGSGSGTSYSLTISRMEAEDAATYYCQQRSTYPTFGGGTKLEIK
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	35	546
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPYTFGGGTKLEIK
DIQMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQKQGKSPQLLVYNAKTLAD	36	547
GVPSRFSGSGSGTQYSLKINSLQPEDFGSYYCQHFWSTPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	37	548
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPYTFGGGTKLEIK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	38	549
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPLTFGGGTKLEIKR
DIKMTQSPSSMYASLGERVTITCKASQDINGYLSWYQQKPGKSPQTLLYRANRLVD	39	550
GVPSRFRGSGSGQDYTLTISSLEYEDMGTYYCLQYDEFPPTFGGGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWYQQKPGKSPKTLIYRAKRLVDG	40	551
VPSRFSGSGSGQDYTLTISSLEYEDMGTYYCLQYDEFPPTFGGGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINGYLSWFQQKPGKSPQTLLYRANRLVD	41	552
GVPSRFRGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRAKRLVDG	42	553
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	43	554
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLHYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	44	555
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	45	556
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	46	557
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	47	558
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	48	559
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFHQKPGKSPKTLIYRANRLVDG	49	560
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	50	561
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	51	562
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	52	563
VPSRFSGSGSGQDYSLTISSLEYEDMGFYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSIYASLGERVTITCKASQDINSYLNWFQQKPGKSPKTLIYRANRLVDGV	53	564
PSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGVGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	54	565
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	55	566
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGCGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	56	567
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGCGTKLELKR
DIQMTQSPASLSVSVGETVTITCRASDNIYSNLAWYQQKQGKSPQLLVYAATNLAD	57	568
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIKR
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVFAATYLADG	58	569
VPSRFSGSGSGTQYSLKINSLQSEDFGNYYCQHFWGTPWTFGGGTKLEIKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	59	570
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGAKLELKR
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	60	571
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIKR
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	61	572
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIKR
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	62	573
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIKR
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	63	574
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	64	575
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLYTFGGGTKLEIKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWFQQKSGTSPKRWIYDTSKLASG	65	576
VPARFSGSGSGTSYSLTFSSMEAEDAATYYCQQWSSNPLYTFGGGTKLEIKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	66	577
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	67	578
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPQLLIYAAS	68	579
NLQSGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	69	580
NLESGIPARFGGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELKR
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	70	581
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	71	582
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNKDPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	72	583
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNKDPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	73	584
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	74	585
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNKDPFTFGAGTKLELKR
DIVLTQSPSSLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	75	586
NLESGIPARFSGSGSGTDFTLTIHPVEEEDAATYYCQQSNKDPFTFGGGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	76	587
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNKDPFTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQAPKLLIKYASN	77	588
LESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWEIPLTFGAGAKLELKR
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQPPKLLIKYASN	78	589
LESGVPARFSGSGSGTDFTLNVHPVEEEDTATYYCQHSWEIPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQPPKLLIKYASN	79	590
LESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWEIPLTFGAGTKLELKR
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	80	591
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVLR
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	81	592
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVLR
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	82	593
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVLR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	83	594
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELKR
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	84	595
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHWVFGGGTKLTVLR
DIVMTQSPSSLAMSVGQKVTMSCKSSQSLLNSSNQKNYLAWYQQKPGQSPKLLVY	85	596
FASTRESGVPDRFIGSGSGTDFTLTISSVQAEDLADYFCQQHYSTPLTFGAGTKLELK
R
DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGV	86	597
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQDNTLPRTFGGGTKLEIKR
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	87	598
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPYTFGGGTKLEIKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYRQKPGQPPKLLIYAAS	88	599
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIKR
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	89	600
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELKR
QIVLTQSPAIMSASPGEKVTITCSASSSVSYMHWFQQKPGTSPKLWIYSTSNLASGV	90	601
PARFSGSGSGTSYSLTISRMEAEDAATYYCQQRSSFPYTFGGGTKLEIKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	91	602
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPLTFGAGTKLELKR
DIQMTQSPSSLSASLGERVSLTCRASQDIHGYLNLFQQKPGETIKHLIYETSNLDSGV	92	603
PKRFSGSRSGSDYSLIIGSLESEDFADYYCLQYASSPLTFGAGTKLELKR
DIVMTQSHKFMSTSVGDRVSITCKASQDVGTAVAWYQQKPGQSPKLLIYWASTRH	93	604
TGVPDRFTGSGSGTDFTLTISNVQSEDLADYFCQQYSSYPFTFGSGTKLEIKR
SIVMTQTPKFLLVSAGDRVTITCKASQSVSNDVAWYQQKPGQSPKLLIYYASNRYTG	94	605
VPDRFTGSGYGTDFTFTISTVQAEDLAVYFCQQDYTSLPTFGAGTKLEIKR
ETTVTQSPASLSVATGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	95	606
VPSRFSSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPLTFGAGTKLELKR
DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGV	96	607
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPFTFGSGTKLEIKR
DIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGV	97	608
PSRFSGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKLEIKR
DIVMTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYASQSISGIP	98	609
SRFSGSGSGSDFTLSINSVEPEDVGVYYCQNGHSFPWTFGGGTKLEIKR
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	99	610
VPSRFSGSGSGSDYTLTISNLESEDFATYYCLQFYEFPYTFGGGTKLEIKR
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	100	611
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPYTFGGGTKLEIKR
DIQMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQKQGKSPQLLVYNAKTLAD	101	612
GVPSRFSGSGSGTQYSLKINSLQPEDFGSYYCQHFWSTPWTFGGGTKLEIKR
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSYRA	102	613
PGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVLR
DIQMTQSPSSLSASLGERVSLTCRASQEISGYLSWLQQKPDGTIKRLIYAASTLDSGV	103	614
PKRFSGSRSGSDYSLTISSLESEDFADYYCLQYASYPWTFGGGTKLEIKR
DIVMTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYASQSISGIP	104	615
SRFSGSGSGSDFTLSINSVEPEDVGVYYCQNGHSFPYTFGGGTKLEIKR
ENVLTQSPAIMSASLGEKVTMSCRASSSVNYMYWYQQKSDASPKLWIYYTSNLAP	105	616
GVPARFSGSGSGNSYSLTISSMEGEDAATYYCQQFTSSPSTFGCGTKLEIKR
ETTVTQSPASLSMAIGEKVTIRCITNTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	106	617
VPSRFSSSGYGTDFVFTIENMLSEDVADYYCLQSDNLPLTFGCGTKLELKR
QLVLTQSSSASFSLGASAKLTCTLSSQHSTYTIEWYQQQPLKPPKYVMELKKDGSHS	107	618
TGDGIPDRFSGSSSGADRYLSISNIQPEDEAIYICGVGDTIKEQFVYVFGCGTKVTVLG
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	108	619
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGCGTKLELKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	109	620
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLHYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLNWFQQKPGKSPKTLIYRANRLVDG	110	621
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	111	622
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	112	623
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	113	624
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCPQYVESPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	114	625
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	115	626
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFHQKPGKSPKTLIYRANRLVDG	116	627
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	117	628
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPLTFGGGTKLEIK
DIKMTQSPSSMYASLGERVTITCKASQDINGYLSWFQQKPGKSPQTLLYRANRLVD	118	629
GVPSRFRGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	119	630
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	120	631
VPSRFSGSGSGQDYSLTISSLEYEDMGFYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSIYASLGERVTITCKASQDINSYLNWFQQKPGKSPKTLIYRANRLVDGV	121	632
PSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGVGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	122	633
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRAKRLVDG	123	634
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	124	635
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGAKLELK
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	125	636
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIK
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	126	637
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIK
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	127	638
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIK
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	128	639
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPFTFGSGTKLEIK
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	129	640
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYLIHVRFGSGTKLEIK
NIVMTQSPKSMSMSVGERVTLSCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT	130	64:
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYLIHVRFGSGTKLEIK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	131	642
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLYTFGGGTKLEIK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	132	643
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPHVHVFGGGTKLEIK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	133	644
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLYTFGGGTKLEIK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	134	645
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLYTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	135	646
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	136	647
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPQLLIYAAS	137	648
NLQSGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	138	649
NLESGIPARFGGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELK
DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPRLLIHYTSTLQPGI	139	650
PSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDILMYTFGGGTKLEIK
DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPRLLIHYTSTLQPGI	140	651
PSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDILMYTFGGGTKLEIK
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	141	652
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELK
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	142	653
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELK
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	143	654
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELK
ENVLTQSPAIMSASLGEKVTMSCRASSSVNYMYWYQQKSDASPKLWIYYTSNLAP	144	655
GVPARFSGSGSGNSYSLTISSMEGEDAATYYCQQFTSSHTFGGGTKLEIK
ENVLTQSPAIMSASLGEKVTMSCRASSSVNYMYWYQQKSDASPKLWIYYTSNLAP	145	656
GVPARFSGSGSGNSYSLTISSMEGEDAATYYCQQFTSSHTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	146	657
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNKDPLTFGAGTKLELK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	147	658
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	148	659
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNKDPFTFGAGTKLELK
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQAPKLLIKYASN	149	660
LESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWEIPLTFGAGAKLELK
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQPPKLLIKYASN	150	661
LESGVPARFSGSGSGTDFTLNVHPVEEEDTATYYCQHSWEIPLTFGAGTKLELK
DIQMTQTPSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYSTSRLHSGV	151	662
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFGGGTKLEIK
DIQMTQTPSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYSTSRLHSGV	152	663
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNALPWTFGGGTKLEIK
DIQMTQTPSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYSTSRLHSGV	153	664
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFGGGTKLEIK
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	154	665
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVL
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	155	666
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVL
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	156	667
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVL
ETTVTQSPASLSVATGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	157	668
VPSRFSSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPFTFGSGTKLEIK
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	158	669
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYFGGGTKVTVL
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	159	670
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLTFGAGTKLELK
DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLIYW	160	671
ASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPPWTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	161	672
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPPTFGGGTKLEIK
DIQMTQSPASLAASVGETVTITCRASENIYYSLAWYQQKQGKSPQLLIYNANSLEDG	162	673
VPSRFSGSGSGTQYSMKINSMQPEDTATYFCKQAYDVPYTFGGGTKLEIK
DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGV	163	674
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQDNTLPRTFGGGTKLEIK
DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGV	164	675
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFGGGTKLEIK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	165	676
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYRQKPGQPPKLLIYAAS	166	677
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNNR	167	678
APGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHWVFGGGTKLTVL
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	168	679
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELK
QLVLTQSSSASFSLGASAKLTCTLSSQHSTYTIEWYQQQPLKPPKYVMELKKDGSHS	169	680
TGDGIPDRFSGSSSGADRYLSISNIQPEDEAIYICGVGDTIKEQFVFVFGGGTKVTVL
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	170	681
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPPTFGGGTKLEIK
DIQMTQSPSSLSASLGERVSLTCRASQDIGISLNWLQQEPDGTIKRLIYATSSLDSGV	171	682
PKRFSGSRSGSDYSLTISSLESEDFVDYYCLQYASSPYTFGGGTKLEIK
DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKNLAD	172	683
GVPSRFSGSGSGTQYSLKINSLQSEDFGYYCQHFWGTPYTFGGGTKLEIK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	173	684
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPLTFGAGTKLELK
DIQMTQSPSSLSASLGERVSLTCRASQDIHGYLNLFQQKPGETIKHLIYETSNLDSGV	174	685
PKRFSGSRSGSDYSLIIGSLESEDFADYYCLQYASSPLTFGAGTKLELK
DIVMTQSHKFMSTSVGDRVSITCKASQDVGTAVAWYQQKPGQSPKLLIYWASTRH	175	686
TGVPDRFTGSGSGTDFTLTISNVQSEDLADYFCQQYSSYPFTFGSGTKLEIK
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNNR	176	687
APGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHLVFGGGTKLTVL
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYVAS	177	688
NLESGIPARFRGSGSGTDFTLNIHPVEEEDAAIYYCQQSHEDPRTFGGGTKLEIK
ENVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSSTSPKLWIYDTSKLASG	178	689
VPGRFSGSGSGNSYSLTISSMEAEDVATYYCFQGSGYPLTFGAGTKLELK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	179	690
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPYTFGGGTKLEIK
ETTVTQSPASLSVATGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	180	691
VPSRFSSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPLTFGAGTKLELK
DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGV	181	692
PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPFTFGSGTKLEIK
DIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGV	182	693
PSRFSGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKLEIK
DIVMTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYASQSISGIP	183	694
SRFSGSGSGSDFTLSINSVEPEDVGVYYCQNGHSFPWTFGGGTKLEIK
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSYRA	184	695
PGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVL
DIQMTQSPSSLSASLGERVSLTCRASQEISGYLSWLQQKPDGTIKRLIYAASTLDSGV	185	696
PKRFSGSRSGSDYSLTISSLESEDFADYYCLQYASYPWTFGGGTKLEIK
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	186	697
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPLPTFGAGTQRELK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	187	698
VPVRFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELK
DIQMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQKQGKSPQLLVYNAKTLAD	188	699
GVPSRFSGSGSGTQYSLKINSLQPEDFGSYYCQHFWSTPWTFGGGTKLEIK
DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLAEG	189	700
VPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGTPFTFGSGTKLEIK
ENVLTQSPAIMSASLGEKVTMSCRASSSVNYMYWSQQKSDASPKLWIYYTSNLAP	190	701
GVPPRFSGSGSGNSYSLTISSMEGEDAATYYCQQFTSSLTFGAGTKLELK
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGSTNNR	191	702
APGVPARFSGSLIGDKSALTITGAQTEDEAIYFCTLWYSNHWVFGGGTKLTVL
DIVMTQSHKFMSTSVGDRVSITCKASQDVGTAVAWYQQKPGQSPKLLIYWASTRH	192	703
TGVPDRFTGSGSGTDFTLTISNVQSEDLADYFCQQYSSYPFTFGSGTKLEIK
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	193	704
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELK
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	194	705
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPFTFGSGTKLEIK
DIVMTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYASQSISGIP	195	706
SRFSGSGSGSDFTLSINSVEPEDVGVYYCQNGHSFPYTFGGGTKLEIK
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNNR	196	707
APGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHWVFGGGTKLTVL
EIFVTQSPASLSMAIGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPGV	197	708
PSRFSSSGYGTDFVFTIENMLSEDVADYYCLQSDNLPLTFGAGTKLELK
QIVLTQSPAIMSASPGEKVTITCSASSSVSYMHWFQQKPGTSPKLWIYSTSNLASGV	198	709
PARFSGSGSGTSYSLTISRMEAEDAATYYCQQRSSYPPTFGSGTKLELK
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	199	710
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGSGTKLEIK
QIVLTQSPAIMSASPGEKVTLTCSASSSVSSSYLYWYQQKPGSSPKLWIYSTSNLASG	200	711
VPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGAGTKLELKR
QLVLTQSSSASFSLGASAKLTCTLSSQHSTYTIEWYQQQPLKPPKYVMELKKDGSHS	201	712
TGDGIPDRFSGSSSGADRYLSISNIQPEDEAIYICGVGDTIKEQFVYVFGGGTKVTVLR
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSN	202	713
RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIKR
DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDG	203	714
VPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPPTFGAGTKLELKR
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSK	204	715
LDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPWTFGGGTKLEIKR
QIVLTQSPAIMSASPGEKVTLPCSASSSVSSSYLYWYQQKPGSSPKLWIYSTSNLASG	205	716
VPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGAGTKLELKR
DVLMTQTPLSLPVSLGDQASISCRSSQSIVYSNGNTYLEWYLQKPGQSPKLLIYKVSN	206	717
RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPPTFGGGTKLEIKR
DIQMTQSPASLSVSVGETVTITCRASENIYNNLAWYQQKQGKSPQLLVYAATNLAD	207	718
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIKR
QIVLTQSPAIMSASPGEKVTLTCSASSSVSSSYLYWYQQKPGSSPKLWIYSTSNLASG	208	719
VPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGAGTKLELKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMYWYQQKPGSSPRLLIYDTSNLASGV	209	720
PVRFSGSGSGTSYSLTISRMEAEDAATYYCQQWSTYPPITFGAGTKLELKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMYWYQQKPGSSPRLLIYDTSNLASGV	210	721
PVRFSGSGSGTSYSLTISRMEAEDAATYYCQQWSSYPFTFGSGTKLEIKR
QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYATSNLASG	211	722
VPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSSNPYTFGGGTKLEIKR
DIQMTQSPASLSVSVGETVTITCRASENIYSNLAWYQQKQGKSPQLLVYAATNLAD	212	723
GVPSRFSGSGSGTQYSLKINSLQSEDFGSYYCQHFWGTPWTFGGGTKLEIKR
DIVMTQSHKFMSTSVGDRVSITCKASQDVSTAVAWYQQKPGQSPKLLIYWASTRH	213	724
TGVPDRFTGSGSGTDYTLTISSVQAEDLALYYCQQHYSTPWTFGGGTKLEIKR
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSK	214	725
LDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPWTFGGGTKLEIKR
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKFLIYKVS	215	726
NRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPPTFGGGTKLEIKR
ETTVTQSPASLSVATGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	216	727
VPSRFSSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPLTFGGGTKLEIKR
DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPRLLIHYTSTLQPGI	217	728
PSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDNLYMYTFGGGTKLEIKR
DIQMNQSPSSLSASLGDTITITCHASQNINVWLSWYQQKPGNIPKLLIYKASNLHTG	218	72
VPSRFSGSGSGTGFTLTISSLQPEDIATYYCQQGQSYPYTFGGGTKLEIKR
QIVLTQSPALMSASPGEKVTMTCSASSSVSYMYWYQQKPRSSPKPWIYLTSNLASG	219	730
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPPTFGGGTKLEIKR
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSK	220	731
LDSGVPDRFTGSGSGTDFTLKISRVEAEDLGFYYCWQGTHFPWTFGGGTKLEIKR
QIVLTQSPAIMSASPGEKVTMTCSASLSVSDMYWYQQKPGSSPRLLIYDTSNLASGV	221	732
PVRFSGSGSGTSYSLTISRMEAEDAATYYCQQWSSYPFTFGSGTKLEIKR
QIVLTQSPAIMSASPGEKVTLTCSASSSVSSSYLYWYQQRPGSSPKLWIYSTSNLASG	222	733
VPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGAGTKLELKR
ENVLTQSPAIMSASLGEKVTMSCRASSSVNYMYWYQQKSDASPKLWIYYTSNLAP	223	734
GVPARFSGSGSGNSYSLTISSMEGEDAATYYCQQFTSSPSTFGGGTKLEIKR
ETTVTQSPASLSMAIGEKVTIRCITNTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	224	735
VPSRFSSSGYGTDFVFTIENMLSEDVADYYCLQSDNLPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	225	736
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIKR
DIVLTQSPATLSVTPGDSVSLSCRASQSISNNLHWYQQKSHESPRLLIKYASQSISGIP	226	737
SRFSGSGSGTDFTLSINSVETEDFGMYFCQQSNSWPFTFGSGTKLEIKR
QIVLTQSPAIMSASPGEKVTLTCSASSSVSSSYLYWYQQKPGSSPKLWIYSTSNLASG	227	738
VPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGGGTKLEIKR
ETTVTQSPASLSVATGEKVTIRCITSTDIDDDMNWYQQKPGEPPKLLISEGNTLRPG	228	739
VPSRFSSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPLTFGAGTKLELKR
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLHWLLQRPGQSPKRLIYLVSK	229	740
LDSGVPDRFTGSGSGTDFTLKISRVEAEDLAVYYCWQGTHFPWTFGGGTKLEIKR
DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPRLLIHYTSTLQPGI	230	741
PSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDNLRTFGGGTKLEIKR
QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIVGTNNR	231	742
APGVPARFSGSLIGDKAALTITGAQTEDEAIYFCVLWYSNHLVFGGGTKLTVLG
NIVMTQSPKSMSMSVGERVTLSCKASENVGTYVSWYQQKPEQSPKLLIYGASNRYT	232	743
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQSYSYPPTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCRASETVDSYGYSFMHWYQQKPGQPPKLLIYRASN	233	744
LESGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPRTFGGGTKLEIKR
DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSTNQKNYLAWYQQKPGQSPKLLLYW	234	745
ASTRESGVPDRFTGSGSGTDFTLTINSVKAEDLAVYYCQQYYSYRTFGGGTKLEIKR
DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSK	235	746
LDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPFTFGSGTKLEIKR
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAAS	236	747
NLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPFTFGSGTKLEIKR
QLVLTQSSSASFSLGASAKLTCTLSSQHSTYTIEWYQQQPLKPPKYVMELKKDGSHS	237	748
TGDGIPDRFSGSSSGADRYLSISNIQPEDEAIYICGVGDTIKEQFVYVFGGGTKVTVLG
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	238	749
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKR
EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEG	239	750
VPSRFSGSGSGSDYSLTISNLESEDFADYYCLQFYEFPLTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCRASESVDNYGISFMNWFQQKPGQPPKLLIYAASN	240	751
QGSGVPARFSGSGSGTDFSLNIHPMEEDDTAMYFCQQSKEVPPTFGGGTKLEIKR
DIVMTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYASQSISGIP	241	752
SRFSGSGSGSDFTLSINSVEPEDVGVYYCQNGHSFPLTFGAGTKLELKR
DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGDTYLEWYLQKPGQSPKLLIYKVSN	242	753
RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPLTFGAGTKLELKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	243	754
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKR
DIVMTQSPTFLAVTASKKVTISCTASESLYSSKHKVHYLAWYQKKPEQSPKLLIYGAS	244	755
NRYIGVPDRFTGSGSGTDFTLTISSVQVEDLTHYYCAQFYSYPYTFGGGTKLEIKR
QLVLTQSSSASFSLGASAKLTCTLSSQHSTYTIEWYQQQPLKPPKYVMELKKDGSHS	245	756
TGDGIPDRFSGSSSGADRYLSISNIQPEDEAIYICGVGDTIKEQFVYVFGGGTKVTVLG
DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQQKPGQPPKLLIKYASN	246	757
LESGVPARFSGSGSGTDFTLNIHPVEEEDTATYYCQHSWEIPLTFGAGTKLELKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	247	758
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKR
DIQMTQSSSYLSVSLGGRVTITCKASDHINNWLAWYQQKPGNAPRLLISGATSLET	248	759
GVPSRFSGSGSGKDYTLSITSLQTEDVATYYCQQYWSTPLTFGAGTKLELKR
DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLAEG	249	760
VPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGTPYTFGGGTKLEIKR
DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLAEG	250	761
VPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGTPPTFGGGTKLEIKR
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASG	251	762
VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPPTFGAGTKLELKR
DIVLTQSPASLAVSLGQRATISCRASESVDNYGISFMNWFQQKPGQPPKLLIYAASN	252	763
QGSGVPARFSGSGSGTDFSLNIHPMEEDDTAMYFCQQSKEVPPTFGGGTKLEIKR
DIVMTQSPTFLAVTASKKVTISCTASESLYSSKHKVHYLAWYQKKPEQSPKLLIYGAS	253	764
NRYIGVPDRFTGSGSGTDFTLTISSVQVEDLTHYYCAQFYSYPYTFGGGTKLEIKR
QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNR	254	765
APGVPVRFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVLG
QIVLTQSPAIMSASPGEKVTMTCSASSSISYMHWYQQKPGTSPKRWIYDTSKLASG	255	766
VPARFSGSGSGTSYSLTISSMEAEDAATYYCHQRSSYPTFGAGTKLELKR
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	257	9577
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPWTFGCGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQDIGDYLAWYQQKPGKAPKLLIYDASSLQSG	258	9578
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGCGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASNLQSG	259	9579
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGCGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQGIASYLAWYQQKPGKAPKLLIYAASTLQPG	260	9580
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFDSYPITFGQGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSG	261	9581
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPYIFGQGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYKASSLESGV	262	9582
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPFTFGQGTRLEIKR
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYDASNLETG	263	9583
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	26	9584
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPWTFGQGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYDASNLETG	265	9585
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV	266	9586
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYKASSLETG	267	9587
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFSSPLTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQNVNTWLAWYQQKPGKAPKLLIYEASSLQS	268	9588
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPFTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISDWLAWYQQKPGKAPKLLIYAASSLQSG	269	9589
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQHNHYPYTFGQGTRLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	270	9590
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPFTFGQGTKVEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	271	9591
STRASGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQAIRDDLGWYQQKPGKAPKLLIYDASHLEAG	272	9592
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPITFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCRASQGVGNDLAWYQQKPGKAPKLLIYAASTLQT	273	9593
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASSFPLTFGPGTKVDIK
DIQMTQSPSSLSASVGDRVTITCRASQIIGTNLAWYQQKPGKAPKLLIYAASSLQSG	274	9594
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTFPVTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYDASSLESG	275	9595
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSNNKNYLAWYQQKPGQPPKLLIYW	276	9596
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYGSPLTFGPGTKVDIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	277	9597
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSSPPTFGQGTRLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	278	9598
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSSPPTFGGGTKVEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	279	9599
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPWTFGQGTKVEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	280	9600
STRASGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYGSPPTFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCQASQDIRNYLNWYQQKPGKAPKLLIYDASTLQSG	281	9601
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPWTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYNASNLETG	282	9602
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPFTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCQASQSISTWLAWYQQKPGKAPKLLIYAASTLRSG	283	9603
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHYTYPLTFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCRASEDISTYLAWYQQKPGKAPKLLIYAASTLQSGV	284	9604
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHTIPWTFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCRASHHISDFLNWYQQKPGKAPKLLIYAASTLQSG	285	9605
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPYTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQDIGDYLAWYQQKPGKAPKLLIYDASSLQSG	286	9606
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQDIRSYLAWYQQKPGKAPKLLIYAASSLQSG	287	9607
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTAPPTFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCRASQDISNNLNWYQQKPGKAPKLLIYAASTLQSG	288	9608
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNTYPLTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQDISNWLAWYQQKPGKAPKLLIYDASSLQS	289	9609
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQGIANYLAWYQQKPGKAPKLLIYAASSLQSG	290	9610
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQADSFPLTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQGIASYLAWYQQKPGKAPKLLIYAASTLQPG	291	9611
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFDSYPITFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASRLQSG	292	9612
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSIIPFTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSG	293	9613
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPYTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSIGRWLAWYQQKPGKAPKLLIYDASNLET	294	9614
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPRTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSINSWLAWYQQKPGKAPKLLIYDTSSLQSG	295	9615
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPYTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSG	296	9616
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPYIFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV	297	9617
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTDSIPITFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQSGV	29	9618
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPYTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQTIRSYLNWYQQKPGKAPKLLIYKASSLESGV	299	9619
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYTIPITFGPGTKVDIK
DIQMTQSPSSLSASVGDRVTITCRASQTISNWLAWYQQKPGKAPKLLIYAASTLQSG	300	9620
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQYIGSYLNWYQQKPGKAPKLLIYDASNLETG	301	9621
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVDSYPLTFGGGTKVEIK
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSN	302	9622
RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPPTFGQGTKLEIK
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYFGSN	303	9623
RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQAPVSFGQGTRLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	304	9624
SSRQSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGQGTKVEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVSSSSYNKNYLAWYQQKPGQPPKLLIYW	30	9625
ASVRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPITFGQGTRLEIK
DIVMTQSPDSLAVSLGERATINCKSTQNVLSSSNNNSYLAWYQQKPGQPPKLLIYW	306	9626
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFTFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCQASQDIGNYLNWYQQKPGKAPKLLIYAASSLQS	607	9627
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYNTPLTFGGGTKLEIK
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYEASTLQSG	608	9628
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK
DIQMTQSPSSLSASVGDRVTITCQASQDISTWLAWYQQKPGKAPKLLIYRASTLESG	609	9629
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQNINNYLNWYQQKPGKAPKLLIYAASRLQSG	310	9630
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPVTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQNINTWLAWYQQKPGKAPKLLIYAASSLQS	311	9631
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPFTFGPGTKVDIK
DIQMTQSPSSLSASVGDRVTITCRASQRIGNYLNWYQQKPGKAPKLLIYAASSLQSG	312	9632
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYAASTLQSGV	313	9633
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYRTVTFGQGTRLEIK
EIVMTQSPATLSVSPGERATLSCRASQSVGSYLAWYQQKPGQAPRLLIYGASTRATG	314	9634
IPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYDSSSQTFGQGTKVEIK
EIVMTQSPATLSVSPGERATLSCRASRSVSTYLAWYQQKPGQAPRLLIYGASTRATGI	315	9635
PARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYDGSPYTFGQGTKLEIK
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYDAS	316	9636
NLETGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPAFGPGTKVDIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNFLAWYQQKPGQPPKLLIYWA	317	9637
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPPTFGQGTKVEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNFLAWYQQKPGQPPKLLIYWA	318	9638
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSDPITFGQGTKLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	319	9639
SARESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSIPIAFGQGTRLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	320	9640
STRDSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSIPYTFGQGTKLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSTSYNKNYLAWYQQKPGQPPKLLIYW	321	9641
ASTRASGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPPTFGQGTKVEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLSTSYNRNFLAWYQQKPGQPPKLLIYW	322	9642
ASTRQSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKLEIK
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYW	323	9643
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSG	324	9644
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASTLQSG	325	9645
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQEADSFPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYDASSLHSG	326	9646
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPWTFGQGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYKASSLESGV	327	9647
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPFTFGQGTRLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSINRWLAWYQQKPGKAPKLLIYSASNLQS	328	9648
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSINTWLAWYQQKPGKAPKLLIYAASSLQSG	329	9649
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPFTFGPGTKVDIK
DIQMTQSPSSLSASVGDRVTITCRASQSIRTWLAWYQQKPGKAPKLLIYDASSLETG	330	9650
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSIRTYLNWYQQKPGKAPKLLIYAASTLQSG	331	9651
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPLTFGGGTKLEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYAASSLHSGV	332	9652
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSITTYLNWYQQKPGKAPKLLIYAASTLQSG	333	9653
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYAASS	334	9654
LQSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQARQTPLTFGQGTRLEIK
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYGASS	335	9655
LQSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQTLQTPFTFGPGTKVDIK
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSD	336	9656
RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGPGTKVDIK
DIVMTQSPDSLAVSLGERATINCKSSQTVFSTSYNKNYLAWYQQKPGQPPKLLIYW	337	9657
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIK
DIVMTQSPDSLAVSLGERATINCKTSQSVFSTSYNRDYLAWYQQKPGQPPKLLIYW	338	9658
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSSPPTFGQGTKVEIK
DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYDASTLQSG	339	9659
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASNLKTG	340	9660
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPTFGGGTKVEIK
EIVMTQSPATLSVSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDTSSRATGI	341	9661
PARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYYDTPYTFGQGTKLEIKR*
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYLA	342	9662
STREPGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPPTFGGGTKLEIKR*
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYVAWYQQKPGQPPKLLIYWA	343	9663
STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAAASLQSG	344	9664
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPWTFGQGTRLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQDINTYLAWYQQKPGKAPKLLIYAASSLQSG	345	9665
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSSFPLTFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSG	346	9666
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLYNFPYTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSISRYLAWYQQKPGKAPKLLIYGASTRESGV	347	9667
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPLTFGQGTKLEIKR
DIQMTQSPSSLSASVGDRVTITCRASQTLSGWLAWYQQKPGKAPKLLIYGASTLQG	348	9668
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPPTFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCFASQDIINYLNWYQQKPGKAPKLLIYEASNLETGV	349	9669
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDVFNLGTG	350	9670
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPFTFGQGTRLEIKR*
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYMASNLES	351	9671
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTNSFPLTFGQGTKLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASNLETGV	352	9672
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR*
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSN	353	9673
RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQSPWTFGQGTKLEIKR*
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYW	354	9674
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSSPLTFGGGTKVEIKR
*
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSN	355	9675
RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPSFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASESVSTWLAWYQQKPGKAPKLLIYKASRLESG	356	9676
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYKTPYTFGQGTKLEIKR*
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYW	357	9677
ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYFTTPLTFGQGTKLEIKR
*
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV	358	9678
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKR*
DIVMTQSPDSLAVSLGERATINCKSSQSVLSSSYNKNYLAWYQQKPGQPPKLLIYWA	359	9679
STRASGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYDTPLTFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYKASTLESGV	360	9680
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNDSIPITFGQGTRLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYDASNLETG	361	9681
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQDYSYPLTFGQGTKVEIKR*
DIVMTQSPDSLAVSLGERATINCKTSQSVFSTSYNRDYLAWYQQKPGQPPKLLIYW	362	9682
ASTRAAGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYYTSTFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSINRYLNWYQQKPGKAPKLLIYAASSLQSG	363	9683
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASNLQSG	364	9684
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSIDSYLNWYQQKPGKAPKLLIYKASTLESGV	365	9685
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQDISTWLAWYQQKPGKAPKLLIYDASNLETG	366	9686
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVNSDPYTFGQGTRLEIKR*
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLESG	367	9687
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGDSLPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSG	368	9688
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSDSFPYTFGQGTKVEIKR*
EIVMTQSPATLSVSPGERATLSCRASQSVSTYLAWYQQKPGQAPRLLIYGASTRATG	369	9689
IPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQHDSYPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSG	370	9690
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGQGTRLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASESISTYLNWYQQKPGKAPKLLIYKASNLESGV	371	9691
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTDSTFITFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASRNIHDYLNWYQQKPGKAPKLLIYAASTLQTG	372	9692
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPPTFGPGTKVDIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSNDSYLNWYQQKPGKAPKLLIYKASTLESG	373	9693
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPLTFGQGTKVEIKR
DIQMTQSPSSLSASVGDRVTITCRASQSISDFLNWYQQKPGKAPKLLIYAASTLQSG	374	9694
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPYTFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSG	375	9695
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANRFPLTFGQGTKLEIKR*
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYKASNLQSG	376	9696
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNFPATFGQGTRLEIKR*
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSN	377	9697
RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPETFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASNLETGV	378	9698
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQGISDYLAWYQQKPGKAPKLLIYDASNLETG	379	9699
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYILPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQDINDFLAWYQQKPGKAPKLLIYAASSLQSG	380	9700
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASKLESG	381	9701
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPWTFGQGTRLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQGIDSWLAWYQQKPGKAPKLLIYAASTLESG	382	9702
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPLTFGGGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQNIGTWLAWYQQKPGKAPKLLIYRASSLESG	383	9703
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPWTFGQGTKLEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQNINNWLAWYQQKPGKAPKLLIYKASTLQS	384	9704
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQADSFPPTFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLAWYQQKPGKAPKLLIYAASTLQSG	385	9705
VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNRYPITFGQGTKVEIKR*
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLAWYQQKPGKAPKLLIYAASILHSGV	386	9706
PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYDSSFITFGQGTRLEIKR*

TABLE 22
CDRs using the Kabat Numbering Scheme
Table 22-Kabat CDR Sequence

HCDR1

HCDR2

HCDR3

Binder		SEQ ID		SEQ ID		SEQ ID
Name	Sequence	NO:	Sequence	NO:	Sequence	NO:
109	SYWIE	1280	EILPGSGSTNYNEKFKG	1794	RAYGYDGGFDY	2308
110	SYWIE	1281	EILPGSGSTNYIEKFKG	1795	RAYGYDEGFDY	2309
111	SYWIE	1282	EILPGSDSTSYNEKFKG	1796	RAYGYDEGFDY	2310
112	IYWIE	1283	EILPGSGSTNYNEKVKG	1797	RAYGYDGGFDY	2311
1	SYWIE	1284	EIFPGSGHTSFNEKFKG	1798	RGYGYDEGFDY	2312
113	SYWIE	1285	EILPGSGSTNYNEKFKG	1799	RGYGYDEGFDY	2313
114	SYWIE	1286	EILPGSGSTNYNEKFKG	1800	RGYGYDEGFDY	2314
115	NYWIE	1287	EILPGSGSTSYNEKFKG	1801	RGYGYDEGFDY	2315
23	SYWIE	1288	EILPGSGSTSYNEKFKG	1802	RGYGYDEGFDY	2316
116	SYWIE	1289	EILPGSGYTSYIEQFKG	1803	RGYGYDEGFDY	2317
117	SYWIE	1290	EILPGSGSTSYNEKFKD	1804	RAYGYDEGFDY	2318
2	SYWIE	1291	EILPGSGSTSYNEKFKG	1805	RGYGYDEGFDY	2319
118	SYWIE	1292	EVLPGSGSTSYNEKFKG	1806	RAYGYDEGFDY	2320
119	SYWIE	1293	EISPGSGSTNYNEKFKG	1807	RGYGYDEGFDY	2321
120	TYWIE	1294	EILPGSGTPNYNEKFKG	1808	RAYGYDAGFDY	2322
121	SYWIE	1295	EILPGSGSTSCNEKFKG	1809	RGYGYDEGFDY	2323
122	SYWIE	1296	EILPGSGRTSYIEKFKG	1810	RGYGYDEGFDY	2324
123	SYWIE	1297	EILPGSGRTSYIEKFKG	1811	RGYGYDEGFDY	2325
38	SYWIE	1298	EILPGSGSTSYNEKFKD	1812	RAYGYDEGFDY	2326
39	SYWIE	1299	EVLPGSGSTSYNEKFKG	1813	RAYGYDEGFDY	2327
40	SYWIE	1300	EILPGSGRTSYIEKFKG	1814	RGYGYDEGFDY	2328
41	SYWIE	1301	EVLPGSGSTSYNEKFKG	1815	RAYGYDEGFDY	2329
42	SYWIE	1302	EILPGSGRTSYIEKFKG	1816	RGYGYDEGFDY	2330
43	SYWIE	1303	EILPGSGSTNYNEKFKG	1817	RAYGYDGGFDY	2331
44	SYWIE	1304	EILPGSDSTSYNEKFKG	1818	RAYGYDEGFDY	2332
45	IYWIE	1305	EILPGSGSTNYNEKVKG	1819	RAYGYDGGFDY	2333
46	SYWIE	1306	EIFPGSGHTSFNEKFKG	1820	RGYGYDEGFDY	2334
47	NYWIE	1307	EILPGSGSTSYNEKFKG	1821	RGYGYDEGFDY	2335
47	NYWIE	1307	EILPGSGSTSYNEKFKG	1821	RGYGYDEGFDY	2335
48	SYWIE	1308	EILPGSGSTSYNEKFKG	1822	RGYGYDEGFDY	2336
48	SYWIE	1308	EILPGSGSTSYNEKFKG	1822	RGYGYDEGFDY	2336
49	SYWIE	1309	EILPGSGYTSYIEQFKG	1823	RGYGYDEGFDY	2337
50	SYWIE	1310	EILPGSGSTSYNEKFKG	1824	RGYGYDEGFDY	2338
51	SYWIE	1311	EISPGSGSTNYNEKFKG	1825	RGYGYDEGFDY	2339
52	TYWIE	1312	EILPGSGTPNYNEKFKG	1826	RAYGYDAGFDY	2340
53	SYWIE	1313	EILPGSGSTSCNEKFKG	1827	RGYGYDEGFDY	2341
54	SYWIE	1314	EILPGSGRTSYIEKFKG	1828	RGYGYDEGFDY	2342
55	NYWIE	1315	EILPGSGSTSYNEKFKG	1829	RGYGYDEGFDY	2343
56	SYWIE	1316	EILPGSGSTSYNEKFKG	1830	RGYGYDEGFDY	2344
3	GYYMH	1317	YISSYNGATSYNQKFKG	1831	GRYGEYFDY	2345
4	GYYMH	1318	YISSYNGVTGYNQKFKG	1832	GRYGDYFDY	2346
5	GYYMH	1319	YISSYNGVTSYNQKFKG	1833	GRYGDYFDY	2347
6	GYYMH	1320	YISSYNGVTGYNQKFKG	1834	GRYGDYFDY	2348
7	GYYMH	1321	YISSYNGANGYNQKFKG	1835	GRYGDYFDY	2349
8	GYYMH	1322	YISSYNGVTGYNQKFKG	1836	GRYGDYFDY	2350
9	GYYMH	1323	YISSYNGVTGYNQKFKG	1837	GRYGDYFDY	2351
10	GYYMH	1324	YISSYNGVTGYNQKFKG	1838	GRYGDYFDY	2352
11	GYYMH	1325	YISSYNGVTGYNQKFKG	1839	GRYGDYFDY	2353
12	GFYMH	1326	YISSYNGATGYNQKFKG	1840	GRYGDYFDY	2354
13	GYYMH	1327	YISSYNGATGYNQKFKG	1841	GRYGDYFDY	2355
57	GYYMH	1328	YISSYNGVTGYNQKFKG	1842	GRYGDYFDY	2356
58	GYYMH	1329	YISSYNGATSYNQKFKG	1843	GRYGEYFDY	2357
124	SYGVH	1330	VIWRGGSTDYNAAFMS	1844	NLYGHYVMDY	2358
125	SYGVH	1331	VIWRGGSTDYNAAFMS	1845	NLYGHYVMDY	2359
126	SYGVH	1332	VIWRGGSTDNNAAFMS	1846	NLYGHYVMDY	2360
127	RYGVH	1333	VIWRGGSTDHNAAFMS	1847	NLYGHYVMDY	2361
128	TYGVH	1334	VIWRGGSTDYNAAFMS	1848	NLYGHYVMDY	2362
129	SYGVH	1335	VIWRGGSTDYNAAFMS	1849	NLYGHYVMDY	2363
130	RYGVH	1336	VIWRGGSTDHNAAFMS	1850	NLYGHYVMDY	2364
59	SYGVH	1337	VIWRGGSTDYNAAFMS	1851	NLYGHYVMDY	2365
60	SYGVH	1338	VIWRGGSTDYNAAFMS	1852	NLYGHYVMDY	2366
61	SYGVH	1339	VIWRGGSTDNNAAFMS	1853	NLYGHYVMDY	2367
62	RYGVH	1340	VIWRGGSTDHNAAFMS	1854	NLYGHYVMDY	2368
63	TYGVH	1341	VIWRGGSTDYNAAFMS	1855	NLYGHYVMDY	2369
131	SYWMH	1342	MIHPNSGSTNYNEKFKS	1856	WGDGYSFAY	2370
132	SYWMH	1343	MIHPNSGSTNYNEKFKS	1857	WGDGYSFAY	2371
133	TYWMH	1344	MIHPNSDNTNYNEKFKS	1858	WGDGYSFAY	2372
14	SYWMH	1345	MIHPNSGTTNYNEKFKS	1859	WGDGYSFAY	2373
134	SYWMH	1346	MIHPNSGNTNYNEKFKS	1860	WGDGYSFAY	2374
64	SYWMH	1347	MIHPNSGSTNYNEKFKS	1861	WGDGYSFAY	2375
65	SYWMH	1348	MIHPNSGTTNYNEKFKS	1862	WGDGYSFAY	2376
135	DYVIN	1349	EIYPGSGSTYYNEKFKG	1863	RGERGPWFAY	2377
136	DYVIN	1350	EIYPGSGSSYYNEKFKG	1864	RGERGPWFAY	2378
137	DYVIN	1351	EIYPGSGSSYYNEKFRG	1865	RGERGPWFAY	2379
138	DYVIN	1352	EIYPGSGSSYYNEKFKG	1866	RGERGPWFAY	2380
15	DYVIN	1353	EIYPGSGSSYYNEKFKG	1867	RGERGPWFAY	2381
66	DYVIN	1354	EIYPGSGSTYYNEKFKG	1868	RGERGPWFAY	2382
67	DYVIN	1355	EIYPGSGSSYYNEKFKG	1869	RGERGPWFAY	2383
68	DYVIN	1356	EIYPGSGSSYYNEKFRG	1870	RGERGPWFAY	2384
69	DYVIN	1357	EIYPGSGSSYYNEKFKG	1871	RGERGPWFAY	2385
24	NYWMN	1358	LIDPSDSETHYNQVFKD	1872	YDVYYRFAY	2386
139	NYWMN	1359	MIDPSDSETHYNQMFKD	1873	YDGYYRFAY	2387
140	NYWMN	1360	MIDPSDSETHFNQMFKD	1874	YDIYYRFAY	2388
16	SYWMH	1361	MIHPNSGSTNYNEKFKS	1875	PGGYGFVY	2389
141	SYWMH	1362	MIHPNSDSTNYNEKFKS	1876	PGGYGFAD	2390
142	TYWMH	1363	MIHPNSGSTNYNEKFKS	1877	PGGYGFTY	2391
143	SYWMH	1364	MIHPNSGSPNYNEKFKS	1878	PGGYGFAY	2392
70	SYWMH	1365	MIHPNSGSPNYNEKFKS	1879	PGGYGFAY	2393
25	SYWIN	1366	NIYPSDSYTNYNQKFKD	1880	GNYIDY	2394
144	SYWIN	1367	NIYPSDSYTNYNQKFKD	1881	GNYIDY	2395
145	DYWIN	1368	NIYPSDSYTNYNQKFKD	1882	GNYIDY	2396
146	DYVIS	1369	EIYPGSGSSYYNEKFKG	1883	PGDLGFAY	2397
147	DYVIS	1370	EIYPGSGSNYYNEKFKG	1884	PGDLGFAY	2398
148	DYVIS	1371	EIYPGSGSSYYNEKFKG	1885	PGDLGFAY	2399
71	DYVIS	1372	EIYPGSGSSYYNEKFKG	1886	PGDLGFAY	2400
72	DYVIS	1373	EIYPGSGSSYYNEKFKG	1887	PGDLGFAY	2401
73	DYVIS	1374	EIYPGSGSNYYNEKFKG	1888	PGDLGFAY	2402
74	DYVIS	1375	EIYPGSGSSYYNEKFKG	1889	PGDLGFAY	2403
74	DYVIS	1375	EIYPGSGSSYYNEKFKG	1889	PGDLGFAY	2403
75	DYVIS	1376	EIYPGSGSSYYNEKFKG	1890	PGDLGFAY	2404
75	DYVIS	1376	EIYPGSGSSYYNEKFKG	1890	PGDLGFAY	2404
76	DYVIS	1377	EIYPGSGSSYYNEKFKG	1891	PGDLGFAY	2405
149	NYGVH	1378	VVWAGGITNYNWALMS	1892	GDGYDDGYAMDY	2406
150	SYGVH	1379	VLWAGGITNYNSALMS	1893	GDGYDDGYAMDY	2407
26	SYGVH	1380	VIWAGGTTNYNSALMS	1894	GDGYDDGYAMDY	2408
77	NYGVH	1381	VVWAGGITNYNWALMS	1895	GDGYDDGYAMDY	2409
78	SYGVH	1382	VLWAGGITNYNSALMS	1896	GDGYDDGYAMDY	2410
79	SYGVH	1383	VIWAGGTTNYNSALMS	1897	GDGYDDGYAMDY	2411
151	SYWMY	1384	MIDPSDSETRLNQKFKD	1898	TRNY	2412
152	SYWMY	1385	MIDPSDSETRLNQKFKD	1899	TRNY	2413
153	SYWMY	1386	MIDPSDSETRLNQKFKD	1900	TRNY	2414
154	DYYMH	1387	WIDPENGDTEYAPKFQG	1901	PLLRYSSAMDY	2415
155	DYYIH	1388	WIDPENGDTEYAPKFQG	1902	PLLRYSSSMDY	2416
156	DYYMH	1389	WIDPENGDTEYAPKFQG	1903	ALLRYSSAMDY	2417
80	DYYMH	1390	WIDPENGDTEYAPKFQG	1904	PLLRYSSAMDY	2418
81	DYYIH	1391	WIDPENGDTEYAPKFQG	1905	PLLRYSSSMDY	2419
82	DYYMH	1392	WIDPENGDTEYAPKFQG	1906	ALLRYSSAMDY	2420
17	DTSLH	1393	RIDPANGNTKYDPKFQG	1907	GPDDGYFYYYSMD	2421
					Y
157	NYYVY	1394	EINPSNGDTNFNEKFKS	1908	YYTHEAYYYAMDC	2422
27	TYYIY	1395	EINPSNGGTNFNEKFKS	1909	YYTHETYYYAMDY	2423
158	DYYMH	1396	RIDPEDGDTEYAPKFQG	1910	YSIYDAMDY	2424
159	DYVIS	1397	EIYPGSGSTYYNEKFKG	1911	RGERGPWFAY	2425
83	DYVIS	1398	EIYPGSGSTYYNEKFKG	1912	RGERGPWFAY	2426
160	DYGMH	1399	VISTYYGDASYNQKFKG	1913	QMDYDYTYYYAMD	2427
					Y
28	SYWMQ	1400	EIDPSDSYTNYNQKFKG	1914	AEYGYGNYPWFAY	2428
84	SYWMQ	1401	EIDPSDSYTNYNQKFKG	1915	AEYGYGNYPWFAY	2429
29	SYWMH	1402	RIHPSDSDTNYNQKFKG	1916	PYYYGGWYFDV	2430
161	DYVIS	1403	EIYPGSGSTYYNEKFKG	1917	MDGPWFAY	2431
30	SYGMS	1404	TISSGGSYTYYPDSVKG	1918	LYDAHWDYFDY	2432
162	TSGMG	1405	SIWNNDNYYNPSLKS	1919	RPYYRYDSFAY	2433
18	NYGMN	1406	WINTYTGEPTYADDFKG	1920	KYYDYEFAY	2434
85	NYGMN	1407	WINTYTGEPTYADDFKG	1921	KYYDYEFAY	2435
163	DYEMH	1408	AIDPETGGTAYNQKFKV	1922	LGDYDVMDY	2436
86	DYEMH	1409	AIDPETGGTAYNQKFKV	1923	LGDYDVMDY	2437
164	SYWMH	1410	EIDPSDSYTNYNQKFKG	1924	AGRYGSSFDY	2438
165	TSGMG	1411	HIYWDDDKRYNPSLKS	1925	RPDDYDGAWFPY	2439
31	SSWMH	1412	EIHPNSGNTNYNEKFKG	1926	YYDYDAYYFDY	2440
87	SSWMH	1413	EIHPNSGNTNYNEKFKG	1927	YYDYDAYYFDY	2441
32	SYWMH	1414	MIHPNSGSTNYNEKFKS	1928	PYYGYDVGY	2442
166	DYVIS	1415	EIYPGSGSNYYNEKFKG	1929	EEKIYFDY	2443
88	DYVIS	1416	EIYPGSGSNYYNEKFKG	1930	EEKIYFDY	2444
167	SYWMH	1417	MIHPNSGSTNYNEKFKS	1931	YDGYWFDY	2445
168	SYWMH	1418	AIYPGNSDTTYNQKFKG	1932	LITTAYYFDY	2446
89	SYWMH	1419	AIYPGNSDTTYNQKFKG	1933	LITTAYYFDY	2447
169	SYWMH	1420	MIHPNSGSTNYNEKFKS	1934	ETGDYGSSYVWYF	2448
					DV
170	DYVIS	1421	EIYPGSGSTYYNEKFKG	1935	GKVTRFAY	2449
171	SYAMS	1422	TISDGGSYTYYPDNVKG	1936	DQDSNWEYFDY	2450
172	DYSMH	1423	WINTETGEPTYADDFKG	1937	ESWDRAMDY	2451
19	SYAMS	1424	TISSGGSYTYYPDSVKG	1938	HEEANWAWFAY	2452
90	SYAMS	1425	TISSGGSYTYYPDSVKG	1939	HEEANWAWFAY	2453
173	NYWMH	1426	MIDPSDSETRLNQQFKD	1940	PYYAMDY	2454
91	NYWMH	1427	MIDPSDSETRLNQQFKD	1941	PYYAMDY	2455
174	SSWMH	1428	EIHPNSGNTNYNEKNKG	1942	YYGNYVWYFDV	2456
92	SSWMH	1429	EIHPNSGNTNYNEKNKG	1943	YYGNYVWYFDV	2457
175	SYWMH	1430	MIHPNSGSTNYNEKFKS	1944	YGSSYWYFDV	2458
93	SYWMH	1431	MIHPNSGSTNYNEKFKS	1945	YGSSYWYFDV	2459
20	SYGVH	1432	VIWSGGSTDYNAAFIS	1946	YYGSSRSYWYLDV	2460
94	SYGVH	1433	VIWSGGSTDYNAAFIS	1947	YYGSSRSYWYLDV	2461
176	SYNMH	1434	ALYSGNGDTSYNQKFK	1948	DYYGSSHLWYFDV	2462
			G
177	TSGMG	1435	HIYWDDDKRYNPSLKS	1949	RAHYDYGWYFDV	2463
178	SYWMH	1436	MIHPNSGSTNYNEKFKS	1950	YDYDWYFDV	2464
33	SYGMS	1437	TISSGGSYTYYPDSVKG	1951	HDDSSYDWFAY	2465
179	SYGMS	1438	TISSGGSYTYYPDSVKG	1952	HEDSNYHYFDY	2466
34	NYWMH	1439	MIHPNSGTTNYNEKFKS	1953	FGDGYHFDY	2467
180	SYGMS	1440	TISSGGSYTYYPDSVKG	1954	QNDSSWAWFAY	2468
95	SYGMS	1441	TISSGGSYTYYPDSVKG	1955	QNDSSWAWFAY	2469
181	SYWMH	1442	MIHPNSGSTNYNEKFKS	1956	PYSNYGWYFDV	2470
96	SYWMH	1443	MIHPNSGSTNYNEKFKS	1957	PYSNYGWYFDV	2471
182	SYWMH	1444	NIDPSDSETHYNQKFKD	1958	DYYGSYWYFDV	2472
97	SYWMH	1445	NIDPSDSETHYNQKFKD	1959	DYYGSYWYFDV	2473
183	DYYMH	1446	RIDPEDGETKYAPKFQG	1960	YGNSAWFAY	2474
98	DYYMH	1447	RIDPEDGETKYAPKFQG	1961	YGNSAWFAY	2475
35	NYGMN	1448	WINTNTGEPTYAEEFKG	1962	WYPYFDY	2476
99	NYGMN	1449	WINTNTGEPTYAEEFKG	1963	WYPYFDY	2477
100	NYGMN	1450	WINTNTGEPTYAEEFKG	1964	WYPYFDY	2478
36	SYWMH	1451	YINPSSGYTKYNQKFKD	1965	SDGSSGNWYFDV	2479
101	SYWMH	1452	YINPSSGYTKYNQKFKD	1966	SDGSSGNWYFDV	2480
184	SYGVH	1453	VIWAGGSTNYNSALMS	1967	EGGYTGYFDV	2481
102	SYGVH	1454	VIWAGGSTNYNSALMS	1968	EGGYTGYFDV	2482
185	SYWMH	1455	NIDPSDSETHYNQKFKD	1969	SNYVPYYAMDY	2483
103	SYWMH	1456	NIDPSDSETHYNQKFKD	1970	SNYVPYYAMDY	2484
186	DYVIS	1457	EIYPGSGSAYYNEKFKG	1971	RGFDY	2485
21	SYGMS	1458	TISSGGSYTYYPDSVKG	1972	HNYSNWDWFAY	2486
187	SYWMH	1459	MIHPNSGSTNYNEKFKS	1973	DYYGSGYGYYFDY	2487
188	SYWMH	1460	MIHPNSGSTNYNEKFKS	1974	DYYGSSYGWYFDV	2488
189	SYWMH	1461	MIHPNSGSTNYNEKFKS	1975	DYYGSSYGWYFDV	2489
190	SYWMH	1462	MIHPNSGSTNYNEKFKS	1976	DYYGSSYGWYFDV	2490
191	SYWMH	1463	MIHPNSGSTNYNEKFKS	1977	DYYGSSYGWYFDV	2491
192	SYWMH	1464	MIHPNSGSTNYNEKFKS	1978	DYYGSGYGWYFD	2492
					V
193	NYWMN	1465	MIDPSDSETHYNQMFKD	1979	YDGYYRFAY	2493
194	NYWMN	1466	MIDPSDSETHFNQMFKD	1980	YDVYYRFAY	2494
195	SYWMH	1467	MIHPNSGSTNYNEKFKS	1981	DYGNYDYAMDY	2495
104	SYWMH	1468	MIHPNSGSTNYNEKFKS	1982	DYGNYDYAMDY	2496
37	SYWMH	1469	MIHPNSGSTNYNEKFKS	1983	DYGNYDYAMDY	2497
196	SYWMH	1470	MIHPNSGSTNYNEKFKS	1984	DYGNYDYAMDY	2498
197	SYGMS	1471	TISSGGSYTYYPDSVKG	1985	QLTGTWYYFDY	2499
198	SYGMS	1472	TISSGGSYTYYPDSVKG	1986	QLTGTWYYFDY	2500
199	SYGMS	1473	TISSGGSYTYYPDSVKG	1987	QLTGTWYYFDY	2501
22	DTSLH	1474	RIDPANGNTKYDPKFQG	1988	GPDDGYFYYYSMD	2502
					Y
200	NYYMS	1475	VINSNGGSTYYPDTVKG	1989	QEGIGYAMDY	2503
201	EYTMH	1476	GIYPNNGGTSYNQKFKG	1990	GGWLLGY	2504
202	SYGVH	1477	VIWSGGSTDYNAAFIS	1991	DGGIRGAMDY	2505
203	SYWIE	1478	EILPGSGSTNYNEKFKG	1992	RGYGYDEGFDY	2506
204	DYEMH	1479	AIDPETGGTAYNQKFKG	1993	NYDYAMDY	2507
205	SYYMS	1480	VINSNGGSTFYPDTVKG	1994	QEGIGYALDY	2508
206	SYAMS	1481	AISSGGSTYYPDSVKG	1995	EREWGVYYGSSLD	2509
					Y
207	DTYMH	1482	RIDPANGNTKYDPKFQG	1996	SDGNYD	2510
208	NYYMS	1483	VINSNGGSTYYPDTVKG	1997	QEGIGYGMDY	2511
209	TYVMN	1484	RIRSKSDNYATYYADSV	1998	HDGVVGFDV	2512
			KD
210	SGYYW	1485	YISYDGSNNYNPSLKN	1999	GGGRG	2513
211	DYSMH	1486	WINTETGEPTYADDFKG	2000	DYYDYYYAMDY	2514
212	DYSMH	1487	WINTETGEPTYADDFKG	2001	ESWDRAMDY	2515
213	NYWMN	1488	RIDPYDSETHYNQKFKD	2002	IYSDYDGAWFAY	2516
214	DYYMD	1489	RVNPYNGGTSYNQKFK	2003	GTVGFAY	2517
			G
215	SYAMS	1490	SISSGGSTYYPDSVKG	2004	EREWGVFYGSSLD	2518
					Y
216	SYAMS	1491	TISSGGSYTYYPDSVKG	2005	HDDSSYGYFDY	2519
217	NYAMS	1492	SISSGGTTYYPDSVKG	2006	TMPDV	2520
218	SYGVH	1493	VIWAGGSTNYNSALMS	2007	DTDGYYWAMDY	2521
219	SDHAW	1494	YISYSGSTTYNPSLKS	2008	KWGDY	2522
220	DYEMH	1495	AIDPETGGTAYNQKFKG	2009	NYDYALDY	2523
221	SGYYW	1496	YISYDGSNDYNPSLKN	2010	GGGRG	2524
222	NYYMS	1497	VINSNGGSTYYPDTVKG	2011	QEEIGYAMDY	2525
223	DYFMH	1498	WIDPETDNTIYDPKFQG	2012	SGNMGFTY	2526
105	DYFMH	1499	WIDPETDNTIYDPKFQG	2013	SGNMGFTY	2527
224	SYAMS	1500	TISSGGSYTYYPDSVKG	2014	QGGSSWGAMDY	2528
106	SYAMS	1501	TISSGGSYTYYPDSVKG	2015	QGGSSWGAMDY	2529
225	SYAMS	1502	TISNGGSYTYYPDSVKG	2016	HEITTRFAY	2530
226	SGYYW	1503	YMSYDGSNNYNPSLKN	2017	EAGYFDY	2531
227	TYAMN	1504	RIRSKSNNYATYYADSV	2018	QYGYDFDY	2532
			KD
228	SYGMS	1505	TISSGGSYTYYPDSVKG	2019	HKGVNWDYFDY	2533
229	DYEMH	1506	AIDPETGGTAYNQKFKG	2020	GDGNYDSWYFDV	2534
230	SYAMS	1507	TISSGGSYTYYPDSVKG	2021	LPVTTVVFDY	2535
231	SYAMS	1508	TISSGGSYTYYPDSVKG	2022	RPVVVPFDY	2536
232	SYGVH	1509	VIWSGGSTDYNAAFIS	2023	GWDADYFDY	2537
233	NYWMH	1510	MIHPNSGSTNYNEKFKS	2024	YDYDDY	2538
234	DYYMN	1511	DINPNNGGTSYNQKFKG	2025	SELGLYAMDY	2539
235	GYWIE	1512	EILPGSGSTNYNEKFKG	2026	GRIHYFDY	2540
236	GYWIE	1513	EILPGSGSTNYNEKFKG	2027	GRIHYFDY	2541
237	SYGVH	1514	VIWSGGSTDYNAAFIS	2028	KGYGYDWYFDV	2542
107	SYGVH	1515	VIWSGGSTDYNAAFIS	2029	KGYGYDWYFDV	2543
238	SYWMH	1516	EIDPSDSYTNYNQKFKG	2030	SSYYYYAMDY	2544
108	SYWMH	1517	EIDPSDSYTNYNQKFKG	2031	SSYYYYAMDY	2545
239	SGYYW	1518	YISYDGSNNYNPSLKN	2032	GGGRD	2546
240	SYGVH	1519	VIWSGGSTDYNAAFIS	2033	GGDYDSYAMDY	2547
241	SYWIT	1520	DIYPGSGSTNYNEKFKS	2034	ESVYDGYSWYFDV	2548
242	DYNMN	1521	VINPNYGTTSYNQKFKG	2035	TYDYDDWYFDV	2549
243	SYWMH	1522	EIDPSDSYTNYNQKFKG	2036	SGNYLYAMDY	2550
244	DYNMN	1523	VINPNYGTTSYNQKFKG	2037	EGTSWYFDV	2551
245	SYGVH	1524	VIWRGGSTDYNAAFMS	2038	KGDGYDWYFDV	2552
246	SYGVH	1525	VIWSGGSTDYNAAFIS	2039	EGNYGSSYDAMDY	2553
247	SYWMH	1526	EIDPSDSYTNYNQKFKG	2040	SSNYPYAMDY	2554
248	NTYMH	1527	RIDPANGNTKYAPKFQG	2041	YSGLY	2555
249	SYWMH	1528	NIDPSDSETHYNQKFKD	2042	RGQIYYGYSWFAY	2556
250	DYYMN	1529	DINPNNGGTSYNQKFKG	2043	STVVADWYFDV	2557
251	SYGIS	1530	EIYPRSGNTYYNEKFKG	2044	SGSSYGYFDV	2558
252	SYGVH	1531	VIWSGGSTDYNAAFIS	2045	KGGYDAYAMDY	2559
253	DYNMN	1532	VINPNYGTTSYNQKFKG	2046	EGFITTVVAVDY	2560
254	DYEMH	1533	AIDPETGGTAYNQKFKG	2047	EGNYDAMDY	2561
255	SYWMH	1534	VIDPSDSYTNYNQKFKG	2048	WDYYGVDY	2562
256	GYWMY	1535	AISPGGGSTYYPDSVKG	2049	SLTATHTYEYDY	2563
388	FNAMG	14116	TIARAGATKYADSVKG	14117	RVFDLPNDY	14118
389	SYSMG	9249	AISWSGDETSYADSVKG	9252	DRWWRPAGLQWDY	9255
390	FNAMG	9250	TIARAGATKYADSVKG	9253	RVFDLPNDY	9256
391	VMG		AVRWSSTGIYYTQYADSVKS	9254	DTYNSNPARWDGYDF	9257

LCDR1

LCDR2

LCDR3

Binder		SEQ ID		SEQ ID		SEQ ID
Name	Sequence	NO:	Sequence	NO:	Sequence	NO:
109	KASQDIN-	5644	RANRLVD	6154	LHYDEFPPT	6664
	SYLS
110	KASQDIN-	5645	RANRLVD	6155	LQYDEFPPT	6665
	SYLN
111	KASQDIN-	5646	RANRLVD	6156	LQYDEFPPT	6666
	SYLS
112	KASQDIN-	5647	RANRLVD	6157	LQYDEFPPT	6667
	SYLS
1	KASQDIN-	5648	RANRLVD	6158	LQYDEFPPT	6668
	SYLS
113	KASQDIN-	5649	RANRLVD	6159	PQYVESPPT	6669
	SYLS
114	KASQDIN-	5650	RANRLVD	6160	LQYDEFPPT	6670
	SYLS
115	KASQDIN-	5651	RANRLVD	6161	LQYDEFPPT	6671
	SYLS
23	KASQDIN-	5652	RANRLVD	6162	LQYDEFPPT	6672
	SYLS
116	KASQDIN-	5653	RANRLVD	6163	LQYDEFPPT	6673
	SYLS
117	KASQDIN-	5654	RANRLVD	6164	LQYDEFPLT	6674
	SYLS
2	KASQDIN-	5655	RANRLVD	6165	LQYDEFPPT	6675
	SYLS
118	KASQDIN-	5656	RANRLVD	6166	LQYDEFPPT	6676
	GYLS
119	KASQDIN-	5657	RANRLVD	6167	LQYDEFPPT	6677
	SYLS
120	KASQDIN-	5658	RANRLVD	6168	LQYDEFPPT	6678
	SYLS
121	KASQDIN-	5659	RANRLVD	6169	LQYDEFPPT	6679
	SYLN
122	KASQDIN-	5660	RANRLVD	6170	LQYDEFPPT	6680
	SYLS
123	KASQDIN-	5661	RAKRLVD	6171	LQYDEFPPT	6681
	SYLS
38	ASQDIN-	5662	RANRLVD	6172	LQYDEFPLT	6682
	SYLS
39	ASQDIN-	5663	RANRLVD	6173	LQYDEFPPT	6683
	GYLS
40	ASQDIN-	5664	RAKRLVD	6174	LQYDEFPPT	6684
	SYLS
41	ASQDIN-	5665	RANRLVD	6175	LQYDEFPPT	6685
	GYLS
42	ASQDIN-	5666	RAKRLVD	6176	LQYDEFPPT	6686
	SYLS
43	ASQDIN-	5667	RANRLVD	6177	LHYDEFPPT	6687
	SYLS
44	ASQDIN-	5668	RANRLVD	6178	LQYDEFPPT	6688
	SYLS
45	ASQDIN-	5669	RANRLVD	6179	LQYDEFPPT	6689
	SYLS
46	ASQDIN-	5670	RANRLVD	6180	LQYDEFPPT	6690
	SYLS
47	ASQDIN-	5671	RANRLVD	6181	LQYDEFPPT	6691
	SYLS
48	ASQDIN-	5672	RANRLVD	6182	LQYDEFPPT	6692
	SYLS
49	ASQDIN-	5673	RANRLVD	6183	LQYDEFPPT	6693
	SYLS
50	ASQDIN-	5674	RANRLVD	6184	LQYDEFPPT	6694
	SYLS
51	ASQDIN-	5675	RANRLVD	6185	LQYDEFPPT	6695
	SYLS
52	ASQDIN-	5676	RANRLVD	6186	LQYDEFPPT	6696
	SYLS
53	ASQDIN-	5677	RANRLVD	6187	LQYDEFPPT	6697
	SYLN
54	ASQDIN-	5678	RANRLVD	6188	LQYDEFPPT	6698
	SYLS
55	ASQDIN-	5679	RANRLVD	6189	LQYDEFPPT	6699
	SYLS
56	ASQDIN-	5680	RANRLVD	6190	LQYDEFPPT	6700
	SYLS
3	RASENIYS	5681	AATYLAD	6191	QHFWGTPWT	6701
	NLA
4	RASENIYS	5682	AATNLAD	6192	QHFWGTPWT	6702
	NLA
5	RASENIYS	5683	AATNLAD	6193	QHFWGSPWT	6703
	NLA
6	RASENIYS	5684	AATNLAD	6194	QHFWGTPWT	6704
	NLA
7	RASENIYS	5685	AATNLAD	6195	QHFWGTPWT	6705
	NLA
8	RASENIYS	5686	AATNVAD	6196	QHFWGTPWT	6706
	NLA
9	RAS-	5687	AATNLAD	6197	QHFWGTPWT	6707
	DNIYSNLA
10	RASENIYS	5688	AATNLAD	6198	QHFWGTPWT	6708
	NLA
11	RASENIYS	5689	AATNLAD	6199	QHFWGTPWT	6709
	NLA
12	RASENIYS	5690	AATYLAD	6200	QHFWGTPWT	6710
	NLA
13	RASENIYS	5691	AATNLAD	6201	QHFWGSPWT	6711
	NLA
57	AS-	5692	AATNLAD	6202	QHFWGTPWT	6712
	DNIYSNLA
58	ASENIYSN	5693	AATYLAD	6203	QHFWGTPWT	6713
	LA
124	KASQDIN-	5694	RANRLVD	6204	LQYDEFPPT	6714
	SYLS
125	KASEN-	5695	GASNRYT	6205	GQSYSYPFT	6715
	VVTYVS
126	KASEN-	5696	GASNRYT	6206	GQSYSYPFT	6716
	VVTYVS
127	KASEN-	5697	GASNRYT	6207	GQSYSYPFT	6717
	VVTYVS
128	KASEN-	5698	GASNRYT	6208	GQSYSYPFT	6718
	VVTYVS
129	KASEN-	5699	GASNRYT	6209	GQSYSYLIH	6719
	VVTYVS
130	KASEN-	5700	GASNRYT	6210	GQSYSYLIH	6720
	VVTYVS
59	ASQDIN-	5701	RANRLVD	6211	LQYDEFPPT	6721
	SYLS
60	ASEN-	5702	GASNRYT	6212	GQSYSYPFT	6722
	VVTYVS
61	ASEN-	5703	GASNRYT	6213	GQSYSYPFT	6723
	VVTYVS
62	ASEN-	5704	GASNRYT	6214	GQSYSYPFT	6724
	VVTYVS
63	ASEN-	5705	GASNRYT	6215	GQSYSYPFT	6725
	VVTYVS
131	SASSSVSY	5706	DTSKLAS	6216	QQWSSNPLY	6726
	MH
132	SASSSVSY	5707	DTSKLAS	6217	QQWSSNPHV	6727
	MH
133	SASSSVSY	5708	DTSKLAS	6218	QQWSSNPLY	6728
	MH
14	SASSSVSY	5709	DTSKLAS	6219	QQWSSNPLY	6729
	MH
134	SASSSVSY	5710	DTSKLAS	6220	QQWSSNPLY	6730
	MH
64	ASSSVSYM	5711	DTSKLAS	6221	QQWSSNPLY	6731
	H
65	ASSSVSYM	5712	DTSKLAS	6222	QQWSSNPLY	6732
	H
135	KASQSVD	5713	AASNLES	6223	QQSNEDPLT	6733
	YD-
	GDSYMN
136	KASQSVD	5714	AASNLES	6224	QQSNEDPLT	6734
	YD-
	GDSYMN
137	KASQSVD	5715	AASNLQS	6225	QQSNEDPLT	6735
	YD-
	GDSYMN
138	KASQSVD	5716	AASNLES	6226	QQSNEDPLT	6736
	YD-
	GDSYMN
15	KASQSVD	5717	AASNLES	6227	QQSNEDPLT	6737
	YD-
	GDSYMN
66	ASQSVDY	5718	AASNLES	6228	QQSNEDPLT	6738
	DGDSYMN
67	ASQSVDY	5719	AASNLES	6229	QQSNEDPLT	6739
	DGDSYMN
68	ASQSVDY	5720	AASNLQS	6230	QQSNEDPLT	6740
	DGDSYMN
69	ASQSVDY	5721	AASNLES	6231	QQSNEDPLT	6741
	DGDSYMN
24	KASQDINK	5722	YTSTLQP	6232	LQYDNLMYT	6742
	YIA
139	KASQDINK	5723	YTSTLQP	6233	LQYDILMYT	6743
	YIA
140	KASQDINK	5724	YTSTLQP	6234	LQYDILMYT	6744
	YIA
16	QATQDIV-	5725	YATELAE	6235	LQFYEFPLT	6745
	KNLN
141	QATQDIV-	5726	YATELAE	6236	LQFYEFPLT	6746
	KNLN
142	QATQDIV-	5727	YATELAE	6237	LQFYEFPLT	6747
	KNLN
143	QATQDIV-	5728	YATELAE	6238	LQFYEFPLT	6748
	KNLN
70	ATQDIV-	5729	YATELAE	6239	LQFYEFPLT	6749
	KNLN
25	RAS-	5730	YTSNLAP	6240	QQFTSSHTF	6750
	SSVNYMY
144	RAS-	5731	YTSNLAP	6241	QQFTSSHTF	6751
	SSVNYMY
145	RAS-	5732	YTSNLAP	6242	QQFTSSHTF	6752
	SSVNYMY
146	KASQSVD	5733	AASNLES	6243	QQSNKDPLT	6753
	YD-
	GDSYMN
147	KASQSVD	5734	AASNLES	6244	QQSNEDPLT	6754
	YD-
	GDSYMN
148	KASQSVD	5735	AASNLES	6245	QQSNKDPFT	6755
	YD-
	GDSYMN
71	ASQSVDY	5736	AASNLES	6246	QQSNKDPLT	6756
	DGDSYMN
72	ASQSVDY	5737	AASNLES	6247	QQSNKDPLT	6757
	DGDSYMN
73	ASQSVDY	5738	AASNLES	6248	QQSNEDPLT	6758
	DGDSYMN
74	ASQSVDY	5739	AASNLES	6249	QQSNKDPFT	6759
	DGDSYMN
75	ASQSVDY	5740	AASNLES	6250	QQSNKDPFT	6760
	DGDSYMN
76	ASQSVDY	5741	AASNLES	6251	QQSNKDPFT	6761
	DGDSYMN
149	RASQSVST	5742	YASNLES	6252	QHSWEIPLT	6762
	SSYSYMH
150	RASQSVST	5743	YASNLES	6253	QHSWEIPLT	6763
	SSYSYMH
26	RASQSVST	5744	YASNLES	6254	QHSWEIPLT	6764
	SSYSYMH
77	ASQSVSTS	5745	YASNLES	6255	QHSWEIPLT	6765
	SYSYMH
78	ASQSVSTS	5746	YASNLES	6256	QHSWEIPLT	6766
	SYSYMH
79	ASQSVSTS	5747	YASNLES	6257	QHSWEIPLT	6767
	SYSYMH
151	RASQDISN	5748	STSRLHS	6258	QQGNTLPWT	6768
	YLN
152	RASQDISN	5749	STSRLHS	6259	QQGNALPWT	6769
	YLN
153	RASQDISN	5750	STSRLHS	6260	QQGNTLPWT	6770
	YLN
154	RSST-	5751	GTSNRAP	6261	ALWYSTHYV	6771
	GAVTTSN
	YAN
155	RSST-	5752	GTSNRAP	6262	ALWYSTHYV	6772
	GAVTTSN
	YAN
156	RSST-	5753	GTSNRAP	6263	ALWYSTHYV	6773
	GAVTTSN
	YAN
80	SST-	5754	GTSNRAP	6264	ALWYSTHYV	6774
	GAVTTSN
	YAN
81	SST-	5755	GTSNRAP	6265	ALWYSTHYV	6775
	GAVTTSN
	YAN
82	SST-	5756	GTSNRAP	6266	ALWYSTHYV	6776
	GAVTTSN
	YAN
17	RASENIYS	5757	AATNLAD	6267	QHFWGTPWT	6777
	NLA
157	IT-	5758	EGNTLRP	6268	LQSDNMPFT	6778
	STDIDDD
	MN
27	MTSIDIDD	5759	EGNTLRP	6269	LQSDNMPFT	6779
	DMN
158	RSST-	5760	GTSNRAP	6270	ALWYSTHYF	6780
	GAVTTSN
	YAN
159	KASQSVD	5761	AASNLES	6271	QQSNEDPLT	6781
	YD-
	GDSYMN
83	ASQSVDY	5762	AASNLES	6272	QQSNEDPLT	6782
	DGDSYMN
160	KSS-	5763	WASTRES	6273	QQYYSYPPW	6783
	QSLLYSTN
	QKNYLA
28	RSST-	5764	GTSNRAP	6274	ALWYSTHWV	6784
	GAVTTSN
	YAN
84	SST-	5765	GTSNRAP	6275	ALWYSTHWV	6785
	GAVTTSN
	YAN
29	RSST-	5766	GTNNRAP	6276	ALWYSNHLF	6786
	GAVTTSN
	YAN
161	KASQSVD	5767	AASNLES	6277	QQSNEDPPT	6787
	YD-
	GDSYMN
30	RSST-	5768	GTNNRAP	6278	ALWYSNHWV	6788
	GAVTTSN
	YAN
162	RASENIYY	5769	NANSLED	6279	KQAYDVPYT	6789
	SLA
18	KSS-	5770	FASTRES	6280	QQHYSTPLT	6790
	QSLLNSSN
	QKNYLA
85	SSQSLLNS	5771	FASTRES	6281	QQHYSTPLT	6791
	SNQKNYL
	A
163	RASQDISN	5772	YTSRLHS	6282	QQDNTLPRT	6792
	YLN
86	ASQDISNY	5773	YTSRLHS	6283	QQDNTLPRT	6793
	LN
164	RASQDISN	5774	YTSRLHS	6284	QQGNTLPWT	6794
	YLN
165	RASENIYS	5775	AATNLAD	6285	QHFWGTPWT	6795
	NLA
31	QATQDIV-	5776	YATELAE	6286	LQFYEFPYT	6796
	KNLN
87	ATQDIV-	5777	YATELAE	6287	LQFYEFPYT	6797
	KNLN
32	SASSSVSY	5778	DTSNLAS	6288	QQWSSYPLT	6798
	MY
166	KASQSVD	5779	AASNLES	6289	QQSNEDPWT	6799
	YD-
	GDSYMN
88	ASQSVDY	5780	AASNLES	6290	QQSNEDPWT	6800
	DGDSYMN
167	RSST-	5781	GTNNRAP	6291	ALWYSNHWV	6801
	GAVTTSN
	YAN
168	QATQDIV-	5782	YATELAE	6292	LQFYEFPLT	6802
	KNLN
89	ATQDIV-	5783	YATELAE	6293	LQFYEFPLT	6803
	KNLN
169	TLSSQHST	5784	GSHSTGD	6294	GVGDTIKEQ	6804
	YTIEWYQ
	Q
170	KASQSVD	5785	AASNLES	6295	QQSNEDPPT	6805
	YD-
	GDSYMN
171	RASQDIGI	5786	ATSSLDS	6296	LQYASSPYT	6806
	SLN
172	RASENIYS	5787	YNAKNLA	6297	QHFWGTPYT	6807
	YL
19	SASSSVSY	5788	STSNLAS	6298	QQRSSFPYT	6808
	MH
90	ASSSVSYM	5789	STSNLAS	6299	QQRSSFPYT	6809
	H
173	KASQDIN-	5790	RANRLVD	6300	LQYDEFPLT	6810
	SYLS
91	ASQDIN-	5791	RANRLVD	6301	LQYDEFPLT	6811
	SYLS
174	RASQDIH	5792	ETSNLDS	6302	LQYASSPLT	6812
	GYLN
92	ASQDIHGY	5793	ETSNLDS	6303	LQYASSPLT	6813
	LN
175	KASQDVG	5794	WASTRHT	6304	QQYSSYPFT	6814
	TAVA
93	ASQDVG-	5795	WASTRHT	6305	QQYSSYPFT	6815
	TAVA
20	KASQSVS	5796	YASNRYT	6306	QQDYTSLPT	6816
	NDVA
94	ASQSVSN-	5797	YASNRYT	6307	QQDYTSLPT	6817
	DVA
176	RSST-	5798	GTNNRAP	6308	ALWYSNHLV	6818
	GAVTTSN
	YAN
177	KASQSVD	5799	VASNLES	6309	QQSHEDPRT	6819
	YD-
	GDSYMN
178	SASSSVSY	5800	DTSKLAS	6310	FQGSGYPLT	6820
	MH
33	IT-	5801	EGNTLRP	6311	LQSDNMPLM	6821
	STDIDDD
	MN
179	RASENIYS	5802	AATNLAD	6312	QHFWGTPYT	6822
	NLA
34	SASSSVSY	5803	STSNLAS	6313	QQRSTYPTF	6823
	MH
180	IT-	5804	EGNTLRP	6314	LQSDNMPLT	6824
	STDIDDD
	MN
95	TSTDIDDD	5805	EGNTLRP	6315	LQSDNMPLT	6825
	MN
181	RASQDISN	5806	YTSRLHS	6316	QQGNTLPFT	6826
	YLN
96	ASQDISNY	5807	YTSRLHS	6317	QQGNTLPFT	6827
	LN
182	SAS-	5808	YTSSLHS	6318	QQYSKLPYT	6828
	QGISNYLN
97	ASQGISNY	5809	YTSSLHS	6319	QQYSKLPYT	6829
	LN
183	RASQSISD	5810	YASQSIS	6320	QNGHSFPWT	6830
	YLH
98	ASQSISDY	5811	YASQSIS	6321	QNGHSFPWT	6831
	LH
35	QATQDIV-	5812	YATELAE	6322	LQFYEFPYT	6832
	KNLN
99	ATQDIV-	5813	YATELAE	6323	LQFYEFPYT	6833
	KNLN
100	ATQDIV-	5814	YATELAE	6324	LQFYEFPYT	6834
	KNLN
36	RASGNIH	5815	NAKTLAD	6325	QHFWSTPWT	6835
	NYLA
101	AS-	5816	NAKTLAD	6326	QHFWSTPWT	6836
	GNIHNYLA
184	RSST-	5817	GTSYRAP	6327	ALWYSTHYV	6837
	GAVTTSN
	YAN
102	SST-	5818	GTSYRAP	6328	ALWYSTHYV	6838
	GAVTTSN
	YAN
185	RASQEIS-	5819	AASTLDS	6329	LQYASYPWT	6839
	GYLS
103	ASQEIS-	5820	AASTLDS	6330	LQYASYPWT	6840
	GYLS
186	KASQSVD	5821	AASNLES	6331	QQSNEDPLP	6841
	YD-
	GDSYMN
21	HASQNIN	5822	KASNLHT	6332	QQGQSYPLT	6842
	VWLS
187	SASSSVSY	5823	DTSKLAS	6333	QQWSSNPLT	6843
	MH
188	RASGNIH	5824	NAKTLAD	6334	QHFWSTPWT	6844
	NYLA
189	RASENIYS	5825	NAKTLAE	6335	QHHYGTPFT	6845
	YLA
190	RAS-	5826	YTSNLAP	6336	QQFTSSLTF	6846
	SSVNYMY
191	RSST-	5827	STNNRAP	6337	TLWYSNHWV	6847
	GAVTTSN
	YAN
192	KASQDVG	5828	WASTRHT	6338	QQYSSYPFT	6848
	TAVA
193	KASQDIN-	5829	RANRLVD	6339	LQYDEFPPT	6849
	SYLS
194	RASENIYS	5830	AATNLAD	6340	QHFWGTPFT	6850
	NLA
195	RASQSISD	5831	YASQSIS	6341	QNGHSFPYT	6851
	YLH
104	ASQSISDY	5832	YASQSIS	6342	QNGHSFPYT	6852
	LH
37	RASENIYS	5833	AATNLAD	6343	QHFWGTPYT	6853
	NLA
196	RSST-	5834	GTNNRAP	6344	ALWYSNHWV	6854
	GAVTTSN
	YAN
197	IT-	5835	EGNTLRP	6345	LQSDNLPLT	6855
	STDIDDD
	MN
198	SASSSVSY	5836	STSNLAS	6346	QQRSSYPPT	6856
	MH
199	SASSSVSY	5837	DTSKLAS	6347	QQWSSNPLT	6857
	MH
22	IT-	5838	EGNSLRP	6348	LQSDNLPLT	6858
	STDIDDD
	MN
200	SASSSVSS	5839	STSNLAS	6349	HQWSSYPPT	6859
	SYLY
201	TLSSQHST	5840	GSHSTGD	6350	GVGDTIKEQ	6860
	YTIEWYQ
	Q
202	RSSQSIVH	5841	KVSNRFS	6351	FQGSHVPWT	6861
	SNGNTYLE
203	KASQDIN-	5842	RANRLVD	6352	LQYDEFPPT	6862
	SYLS
204	KSS-	5843	LVSKLDS	6353	WQGTHFPWT	6863
	QSLLDSDG
	KTYLN
205	SASSSVSS	5844	STSNLAS	6354	HQWSSYPPT	6864
	SYLY
206	RSSQSIVY	5845	KVSNRFS	6355	FQGSHVPPT	6865
	SNGNTYLE
207	RASENI-	5846	AATNLAD	6356	QHFWGTPWT	6866
	YNNLA
208	SASSSVSS	5847	STSNLAS	6357	HQWSSYPPT	6867
	SYLY
209	SASSSVSY	5848	DTSNLAS	6358	QQWSTYPPI	6868
	MY
210	SASSSVSY	5849	DTSNLAS	6359	QQWSSYPFT	6869
	MY
211	RAS-	5850	ATSNLAS	6360	QQWSSNPYT	6870
	SSVSYMH
212	RASENIYS	5851	AATNLAD	6361	QHFWGTPWT	6871
	NLA
213	KASQDVS	5852	WASTRHT	6362	QQHYSTPWT	6872
	TAVA
214	KSS-	5853	LVSKLDS	6363	WQGTHFPWT	6873
	QSLLDSDG
	KTYLN
215	RSSQSIVH	5854	KVSNRFS	6364	FQGSHVPPT	6874
	SNGNTYLE
216	IT-	5855	EGNTLRP	6365	LQSDNMPLT	6875
	STDIDDD
	MN
217	KASQDINK	5856	YTSTLQP	6366	LQYDNLYMY	6876
	YIA
218	HASQNIN	5857	KASNLHT	6367	QQGQSYPYT	6877
	VWLS
219	SASSSVSY	5858	LTSNLAS	6368	QQWSSNPPT	6878
	MY
220	KSS-	5859	LVSKLDS	6369	WQGTHFPWT	6879
	QSLLDSDG
	KTYLN
221	SASLSVSD	5860	DTSNLAS	6370	QQWSSYPFT	6880
	MY
222	SASSSVSS	5861	STSNLAS	6371	HQWSSYPPT	6881
	SYLY
223	RAS-	5862	YTSNLAP	6372	QQFTSSPST	6882
	SSVNYMY
105	ASSSVNY	5863	YTSNLAP	6373	QQFTSSPST	6883
	MY
224	IT-	5864	EGNTLRP	6374	LQSDNLPLT	6884
	NTDIDDD
	MN
106	TNTDIDDD	5865	EGNTLRP	6375	LQSDNLPLT	6885
	MN
225	KASQSVD	5866	AASNLES	6376	QQSNEDPWT	6886
	YD-
	GDSYMN
226	RASQSISN	5867	YASQSIS	6377	QQSNSWPFT	6887
	NLH
227	SASSSVSS	5868	STSNLAS	6378	HQWSSYPPT	6888
	SYLY
228	IT-	5869	EGNTLRP	6379	LQSDNMPLT	6889
	STDIDDD
	MN
229	KSS-	5870	LVSKLDS	6380	WQGTHFPWT	6890
	QSLLDSDG
	KTYLH
230	KASQDINK	5871	YTSTLQP	6381	LQYDNLRTF	6891
	YIA
231	RSST-	5872	GTNNRAP	6382	VLWYSNHLV	6892
	GAVTTSN
	YAN
232	KASEN-	5873	GASNRYT	6383	GQSYSYPPT	6893
	VGTYVS
233	RASET-	5874	RASNLES	6384	QQSNEDPRT	6894
	VDSYGYSF
	MH
234	KSS-	5875	WASTRES	6385	QQYYSYRTF	6895
	QSLLYSTN
	QKNYLA
235	KSS-	5876	LVSKLDS	6386	WQGTHFPFT	6896
	QSLLDSDG
	KTYLN
236	KASQSVD	5877	AASNLES	6387	QQSNEDPFT	6897
	YD-
	GDSYMN
237	TLSSQHST	5878	GSHSTGD	6388	GVGDTIKEQ	6898
	YTIEWYQ
	Q
107	LSSQHSTY	5879	GSHSTGD	6389	GVGDTIKEQFVYV	6899
	TIEWYQQ
238	SASSSVSY	5880	DTSKLAS	6390	QQWSSNPLT	6900
	MH
108	ASSSVSYM	5881	DTSKLAS	6391	QQWSSNPLT	6901
	H
239	QATQDIV-	5882	YATELAE	6392	LQFYEFPLT	6902
	KNLN
240	RAS-	5883	AASNQGS	6393	QQSKEVPPT	6903
	ESVDNY-
	GISFMN
241	RASQSISD	5884	YASQSIS	6394	QNGHSFPLT	6904
	YLH
242	RSSQSIVH	5885	KVSNRFS	6395	FQGSHVPLT	6905
	SNGDTYLE
243	SASSSVSY	5886	DTSKLAS	6396	QQWSSNPLT	6906
	MH
244	TASESLYS-	5887	GASNRYI	6397	AQFYSYPYT	6907
	SKHKVHYL
	A
245	TLSSQHST	5888	GSHSTGD	6398	GVGDTIKEQ	6908
	YTIEWYQ
	Q
246	RASQSVST	5889	YASNLES	6399	QHSWEIPLT	6909
	SSYSYMH
247	SASSSVSY	5890	DTSKLAS	6400	QQWSSNPLT	6910
	MH
248	KASDHIN	5891	GATSLET	6401	QQYWSTPLT	6911
	NWLA
249	RASENIYS	5892	NAKTLAE	6402	QHHYGTPYT	6912
	YLA
250	RASENIYS	5893	NAKTLAE	6403	QHHYGTPPT	6913
	YLA
251	SASSSVSY	5894	DTSKLAS	6404	QQWSSNPPT	6914
	MH
252	RAS-	5895	AASNQGS	6405	QQSKEVPPT	6915
	ESVDNY-
	GISFMN
253	TASESLYS-	5896	GASNRYI	6406	AQFYSYPYT	6916
	SKHKVHYL
	A
254	RSST-	5897	GTSNRAP	6407	ALWYSTHYV	6917
	GAVTTSN
	YAN
255	SASSSI-	5898	DTSKLAS	6408	HQRSSYPTF	6918
	SYMH

HCDR1

HCDR2

HCDR3

Binder		SEQ ID		SEQ ID		SEQ ID
Name	Sequence	NO:	Sequence	NO:	Sequence	NO:
265	SYALS	9968	IINPSGGTNYAQKFQG	10230	DLGDPGMDV	10492
266	NYAIS	9969	IIDPSGGSTTYAQKFQG	10231	DLGDMGMDV	10493
267	NYAFS	9970	IINPSGGSTSYAQKFQG	10232	DVGDRGMDV	10494
263	SYALS	9971	IINPSGGTNYAQKFQG	10233	DLGDPGMDV	10495
268	GYYMH	9972	WIDPNGGGTQYAQKFQG	10234	DIVHDGTEYFQH	10496
269	SYYMH	9973	IINPSGGSTSYAQKFQG	10235	DIVHDGTEYFQH	10497
270	SYAIS	9974	IINPSGGSTNYAQKFQG	10236	EGRDHDAFDI	10498
271	DYGIS	9975	IINPSGGSTSYAQKFQG	10237	EGRSHDAFDI	10499
272	GYYMH	9976	WMNPHSGDTGYAQKFQG	10238	WVGTTEYYYYYYMDV	10500
273	DYYLH	9977	IIDPSGGSTSIAQKFQG	10239	TAYYDFWSGYSMDV	10501
274	SHYMH	9978	IIDPSGGSTSYAQEFQG	10240	DMDNWNTGYYYYMD	10502
					V
275	SYAIN	9979	WVNPNSGDTAYAQKFQG	10241	DQRGGDAWDV	10503
276	NYAIS	9980	IITPSGGSTTYAHKFQG	10242	DTAGHFDI	10504
277	NDVIN	9981	WMNPNSGNTGYAQKFQG	10243	DNPDLDGMDV	10505
278	SYAIN	9982	WISAYNGNTNYAQKFQG	10244	DLVGHFDY	10506
279	SYAIS	9983	WINPNSGGTNYAQKFQG	10245	DGYSGSYSD	10507
264	SYAIS	9984	WINPNSGGTNYAQKFQG	10246	DGYSGSYSD	10508
257	SYAIS	9985	WINPNSGGTNYAQKFQG	10247	DGYSGSYSD	10509
280	SHAIS	9986	IINPSGGSTSYAQKFQG	10248	DQGSSGTFDY	10510
281	SYAIS	9987	WINPNSGGTNYAQKFQG	10249	DSTDVIDY	10511
282	SYDIN	9988	WINPNSGDTKYAQNFQG	10250	DGGTVTPTEEYYYYG-	10512
					MDV
283	SYAIS	9989	WISVYNGNTNYAQNLQG	10251	LDDLDY	10513
284	SYYIH	9990	WINPNNGGTHYAQKFQG	10252	DMVRDSAEYFQH	10514
285	TSYIH	9991	MINPSGGTTTYAQKFQG	10253	DSSGYPIDY	10515
286	SYDIN	9992	GIIPLSGAPNYAHKFQG	10254	GALYNWNDGWFDP	10516
258	SYDIN	9993	GIIPLSGAPNYAHKFQG	10255	GALYNWNDGWFDP	10517
287	SWYMS	9994	GIWYEGSNKYYADSVKG	10256	LGTASLPYFDY	10518
288	GYYMH	9995	WINPNRGDTKYAQKFQG	10257	ESGDGFDP	10519
289	NYYIH	9996	WMNPNSGNTGYAQKFQG	10258	DWPNWFDP	10520
290	DNYIH	9997	WIRSDNGETSYAQKFQG	10259	EVQLVGFDY	10521
291	DHHVH	9998	GIIPIFGTANYAQKFQG	10260	GSSWYLHFQH	10522
260	DHHVH	9999	GIIPIFGTANYAQKFQG	10261	GSSWYLHFQH	10523
292	SYAIY	10000	GIIPIFGTTNYAQKFQG	10262	GVDRYNWNDAFDY	10524
293	DYYMH	10001	WIHSNSGGTHSAQKFQG	10263	ESSGYDSSLDY	10525
294	SYGIS	10002	WINPNSGDTDYAQKFQG	10264	DPRLDSSDPGY	10526
295	NYGIN	10003	WISAYNGNTNYAQKFQG	10265	GGMDV	10527
296	RYGIA	10004	ISYPSDGSTSSAQKLQG	10266	DRLGDLDY	10528
261	RYGIA	10005	ISYPSDGSTSSAQKLQG	10267	DRLGDLDY	10529
297	SYAIS	10006	WMNPNSGNTGYAQKFQG	10268	DSIVGGYPFDY	10530
298	SYDIN	10007	TITPIFGTTDYAQKFQG	10269	EGYSSSWHDDAFDI	10531
299	NYAIS	10008	IIDPSGGSTSYAQKFQG	10270	DLGDYGLDS	10532
300	GYYMH	10009	WMNPNSGDTGYAQRFQG	10271	GGSDSSGYYYEGYFQH	10533
301	SYAIS	10010	YMSPNSGNTGYAQKFQG	10272	DKGGYYDSSGYYWY	10534
302	SYEMH	10011	AISSNGGSTYYADSVKG	10273	VGDGDGYNPDFDY	10535
303	SYGIS	10012	WIDPTSGATDTAHKFQG	10274	DPIVATEVDY	10536
304	SYAIS	10013	WMSPNSGNTGYAQKFQG	10275	DSGAFDI	10537
305	NYAIS	10014	WMNPNSGNTGYAQKFQG	10276	EGLLDAFDI	10538
306	RYGIT	10015	WMNPYDGNTGYAQKFQG	10277	GGRHHDAFDI	10539
307	SYAIS	10016	IINPSGDGTNYAQKFQG	10278	DISNDAFDI	10540
308	GHYMH	10017	WISAYNGDTNYAQKFQG	10279	GSSWDDAFDI	10541
309	NHYTS	10018	AIGAGGGTYYADSVKG	10280	EGWNDDVFDI	10542
310	SYAIS	10019	IINPSAGTTYYAERFQG	10281	DGNFGAFDI	10543
311	TYAIT	10020	EIIPIFGTANYAQKFQG	10282	DKSGWNYGSGSYN-	10544
					DAFDI
312	GYYMH	10021	WMNPNSGKTEYAQKFQG	10283	DGGLDFDY	10545
313	TYYIH	10022	WMNPNTGDTGSAQKFQG	10284	DPAVTPDAFDI	10546
314	SYAIS	10023	IIDPSGGGTSYAQKLQG	10285	SLYYYGMDV	10547
315	SSAIS	10024	GIIPIFGTANYAQKFQG	10286	EDDILPPRAFDI	10548
316	DYAMH	10025	GISGGGGVTYYADSVKG	10287	VYSSGWLDAFDI	10549
317	SYAIS	10026	WISGYNGNTNYAQKFQG	10288	SDVSPDAFDI	10550
318	IYAIT	10027	WVNPNSGNTGYSQKFQG	10289	PTSSSDDAFDI	10551
319	SYAIS	10028	WINPNSGGTNYAQKFQG	10290	ASRGDDAFDI	10552
320	SDDIN	10029	IINPSGGSTSYAQKFQG	10291	ERYEGGY-	10553
					SSGPGNYYYGMDV
321	NYAIS	10030	WMNPNSGNTGYAQKFQG	10292	DDDYGDYPV	10554
322	DHAIN	10031	WMNPKIGNTGYAQKFQG	10293	DSSGYDAFDI	10555
323	SYDIN	10032	RINPGTGGTDYAHKFQG	10294	ETPSDYYDSSGYYYN-	10556
					DAFDI
324	SYAIS	10033	IIIPSGGTNYAQTFQG	10295	DLGTTFDI	10557
325	AYYLH	10034	WINPDNDNAYYAQKFQG	10296	DIAVAALAYGMDV	10558
326	SYAMS	10035	VISYDGSDQYYADSVKG	10297	QSLYYYYGMDV	10559
327	DYYVH	10036	WISTFTGNTDYAQNFQG	10298	DAPLAAAGTDYYYG-	10560
					MDV
262	DYYVH	10037	WISTFTGNTDYAQNFQG	10299	DAPLAAAGTDYYYG-	10561
					MDV
328	SYAMS	10038	FISDDGITKYYADSVKG	10300	DDSSGYGGMDV	10562
329	SYAMH	10039	VISYDGGDKYYADSVKG	10301	GSLVLGYYYMDV	10563
330	NYYIH	10040	WINPNTGGTDYAQKFQG	10302	GGGGSYYDAFDV	10564
331	SYAIS	10041	RINPNSGNTGYAQKFQG	10303	DIGEGYSMDV	10565
332	NHYTS	10042	VISYDGSNKYYADSVKG	10304	EEKYSSSWYVGVDAFDI	10566
333	SSAMH	10043	SISGSGDNAYYADSVKG	10305	DQEDYYYDSSGYGMDV	10567
334	SHAIS	10044	GIIPIFGTANYAQKFQG	10306	GDWGIVVVPAAIGAFDI	10568
335	AYYMH	10045	RISPVFGSTTYAQRFQG	10307	DLGYYDSSGYRYDAFDI	10569
336	SYDIN	10046	GISPMFGTANYAQKFQG	10308	DGWYYGMDV	10570
337	SYGIS	10047	WINPNSGGTKYAQKFQG	10309	GEAGNLDWYFDL	10571
338	NYGIS	10048	WINPNNGDTKYAQKFQG	10310	EDVWYFDL	10572
339	TYGIS	10049	WISTYDGKTNYAQKLQG	10311	HLGGDWYFDL	10573
340	GYYMH	10050	WINPNTGATYYAQKFQG	10312	QHGDYDWYFDL	10574
341	TYYVH	10051	WINPNSGNTGYAQKFQG	10313	DSGRH	10575
342	SYGIS	10052	RIIPMLGIANYAQKFQG	10314	EEVAGANWFDP	10576
343	SYAMN	10053	IINPSGGSTSYARKFQG	10315	EGDYGSGEFDY	10577
344	SSYMH	10054	WMNPRSGNTGYAQKFQG	10316	ERDDYGDYGWLDY	10578
345	GYYMH	10055	IINPSGGSTSYAQKFQG	10317	DLYDSSGY-	10579
					WHYYYYMDV
346	SYAFS	10056	WINPNSGGTNYAQKFQG	10318	FSGYDYVDY	10580
347	SYAIS	10057	IINPNGGNTSYAQKFQG	10319	DVGEDFDL	10581
348	SYYIH	10058	VINPADGDTTYAQMFQG	10320	DFDWLFAMDV	10582
349	NYALN	10059	RINPNGGTTYYAKNFQG	10321	HGDHGFYV	10583
350	SYAIS	10060	MINPNVGSATYAQRFQG	10322	EDSGTSWFDP	10584
351	SYYMH	10061	IINPSDGSTSYAQRFQG	10323	DDRGSNYYYGMDV	10585
352	AYYVH	10062	WMNPNSGTTGYAQKFQG	10324	DSSDYYGDYRADAFDI	10586
353	SYDIN	10063	VISPSGDATLYAQSFQG	10325	GLDH	10587
354	DYGMH	10064	AIGGIGDSTYYADSVKG	10326	MNYGDSNYYYYYG-	10588
					MDV
355	SYDIS	10065	MISPSDGSTTYAPKFQG	10327	GAVGFDY	10589
356	SYGIS	10066	WINTYSGYTDYAHKFQG	10328	DDFLSFGY	10590
357	DYYIH	10067	GIIPYFGTANYAQKFQG	10329	SISGSYVLDAFDI	10591
358	SYGIS	10068	GIIPIFGTANYAQKFQG	10330	DWGYGDYADDAFDI	10592
359	NNDIN	10069	WINPIYGSANYAQNFQG	10331	DWRGFDY	10593
360	EYAIH	10070	RMNPHNGDTGYAQKFQG	10332	EGDYLGYPIDC	10594
361	DYSMS	10071	AIWQDGNVKFYADSVKG	10333	DGNSGYVF	10595
362	TYYMH	10072	WINPNTGDTAYAQKIQG	10334	TAEAVAGLPAFDY	10596
363	NYAID	10073	GIIPLFGTTTYAQKFQG	10335	VTLYGDYDY	10597
364	THWMH	10074	MINPSDGVTYYAQTFQG	10336	EYYGEGFDY	10598
259	THWMH	10075	MINPSDGVTYYAQTFQG	10337	EYYGEGFDY	10599
365	SYAIS	10076	IINPSGGSTSNAQKFQG	10338	DLGDTAMDG	10600
366	SYYLH	10077	IITPSGGSTTYAHKFQG	10339	DGGLASFDY	10601
367	SYAIS	10078	WMNPNSGNTGYAQKFQG	10340	GGGWAMTDAFDI	10602
368	DYGMS	10079	LIYSGGDTYYADSVKG	10341	KEYYYDSSGYLRLFDY	10603
369	DYYMH	10080	GINPIFGTSNYAQKFQG	10342	DISGYDYYYYGMDV	10604
370	NYAFS	10081	MIDPSDGTIAYAQKFQG	10343	SDYDFWSGLGGYFDY	10605
371	SYAIS	10082	TIDPNSGGTMFAQKFQG	10344	DSAEWELGGSFDY	10606
372	NHYTS	10083	SIGVNGDTYYLDSVKG	10345	EGLVFSGRGHWYFDL	10607
373	NYAIS	10084	RINPNGGNTSNAQKFQG	10346	DYEDADFDG	10608
374	DHHVH	10085	WMNPDSGNTGYAQRFQG	10347	DSTSGVDY	10609
375	SYAMS	10086	VISYDGHDQFYADSVKG	10348	GEQQLEGFYYYYGMDV	10610
376	SYWMH	10087	VISYDGSKEYYADSVKG	10349	DYGDYGTYDY	10611
377	SYWMH	10088	GISGGGDDTYYADSVKG	10350	EPLAYCGGDCPGGFDY	10612
378	DHYMD	10089	AIGTGGDTYYADSVKG	10351	HEDTAIFLDY	10613
379	SYYMH	10090	MISPSDGSTTYAPKFQG	10352	DGYDAWSYGMDV	10614
380	GYYMH	10091	WMNPNSGNTGYAQKFQG	10353	DGVTGTDY	10615
381	SYVLH	10092	AISGAGDSTYYADSVKG	10354	EPTTVTDDWYFDL	10616
382	SHWMH	10093	AISGNGDNSYYADSVKG	10355	DRAPEYFDL	10617
383	SYAIS	10094	WINPNSGGTNYAQKFQG	10356	DDYGDYGGGMDV	10618
384	DYYMH	10095	WMNPNSGHTGYAEKFQG	10357	DTSPRYGDGFFDY	10619
385	SYWMH	10096	VTSYDGSNKYYADSVKG	10358	ESGFSAEYFQH	10620
386	SYAIS	10097	IINPSGGSTSYAQKFQG	10359	ATGLYCSGSCFDY	10621

LCDR1

LCDR2

LCDR3

Binder		SEQ ID		SEQ ID		SEQ ID
Name	Sequence	NO:	Sequence	NO:	Sequence	NO:
265	RASQDISN	12194	DASNLET	12454	QQSYSTPLT	12714
	YLN
266	RASQSIS-	12195	AASSLQS	12455	QQSYSTPLT	12715
	SYLN
267	QASQDIS	12196	KASSLET	12456	QQSFSSPLT	12716
	NYLN
263	RASQDISN	12197	DASNLET	12457	QQSYSTPLT	12717
	YLN
268	RASQNVN	12198	EASSLQS	12458	QQANSFPFT	12718
	TWLA
269	RASQSISD	12199	AASSLQS	12459	AQHNHYPYT	12719
	WLA
270	KSS-	12200	WASTRES	12460	QQYYTTPFT	12720
	QSVLSSSY
	NKNYLA
271	KSS-	12201	WASTRAS	12461	QQYYSTPFT	12721
	QSVLSSSY
	NKNYLA
272	RAS-	12202	DASHLEA	12462	QQANSFPIT	12722
	QAIRDDLG
273	RASQGVG	12203	AASTLQT	12463	QQASSFPLT	12723
	NDLA
274	RASQI-	12204	AASSLQS	12464	QQSYTFPVT	12724
	IGTNLA
275	RASQSIST-	12205	DASSLES	12465	QQSYSTPFT	12725
	WLA
276	KSS-	12206	WASTRES	12466	QQYYGSPLT	12726
	QSVLSSS-
	NNKNYLA
277	KSS-	12207	WASTRES	12467	QQYYSSPPT	12727
	QSVLSSSY
	NKNYLA
278	KSS-	12208	WASTRES	12468	QQYYSSPPT	12728
	QSVLSSSY
	NKNYLA
279	KSS-	12209	WASTRES	12469	QQYYSTPWT	12729
	QSVLSSSY
	NKNYLA
264	KSS-	12210	WASTRES	12470	QQYYSTPWT	12730
	QSVLSSSY
	NKNYLA
257	KSS-	12211	WASTRES	12471	QQYYSTPWT	12731
	QSVLSSSY
	NKNYLA
280	KSS-	12212	WASTRAS	12472	QQYYGSPPT	12732
	QSVLSSSY
	NKNYLA
281	QASQDIR	12213	DASTLQS	12473	QQAYSFPWT	12733
	NYLN
282	QASQDIS	12214	NASNLET	12474	QQLNSYPFT	12734
	NYLN
283	QASQSIST	12215	AASTLRS	12475	LQHYTYPLT	12735
	WLA
284	RASEDI-	12216	AASTLQS	12476	QQSHTIPWT	12736
	STYLA
285	RASH-	12217	AASTLQS	12477	QQSYSSPYT	12737
	HISDFLN
286	RASQDIG	12218	DASSLQS	12478	QQANSFPLT	12738
	DYLA
258	RASQDIG	12219	DASSLQS	12479	QQANSFPLT	12739
	DYLA
287	RASQDIRS	12220	AASSLQS	12480	QQSYTAPPT	12740
	YLA
288	RASQDIS-	12221	AASTLQS	12481	LQHNTYPLT	12741
	NNLN
289	RASQDIS-	12222	DASSLQS	12482	QQAISFPLT	12742
	NWLA
290	RASQGIA	12223	AASSLQS	12483	QQADSFPLT	12743
	NYLA
291	RASQGIAS	12224	AASTLQP	12484	QQFDSYPIT	12744
	YLA
260	RASQGIAS	12225	AASTLQP	12485	QQFDSYPIT	12745
	YLA
292	RASQGISN	12226	AASRLQS	12486	QQSSIIPFT	12746
	YLA
293	RASQGISN	12227	AASTLQS	12487	QQAYSFPYT	12747
	YLA
294	RASQSIGR	12228	DASNLET	12488	QQSYSTPRT	12748
	WLA
295	RASQSINS	12229	DTSSLQS	12489	QQTYSTPYT	12749
	WLA
296	RASQSISS	12230	AASTLQS	12490	QQGYSTPYI	12750
	WLA
261	RASQSISS	12231	AASTLQS	12491	QQGYSTPYI	12751
	WLA
297	RASQSIS-	12232	AASSLQS	12492	QQTDSIPIT	12752
	SYLN
298	RASQSIS-	12233	AASTLQS	12493	QQSYSIPYT	12753
	SYLN
299	RASQTIRS	12234	KASSLES	12494	QQTYTIPIT	12754
	YLN
300	RASQTISN	12235	AASTLQS	12495	QQANSFPPT	12755
	WLA
301	RASQYIGS	12236	DASNLET	12496	QQVDSYPLT	12756
	YLN
302	RSSQSLLH	12237	LGSNRAS	12497	MQGTHWPPT	12757
	SNGYNYL
	D
303	RSSQSLLH	12238	FGSNRAS	12498	MQALQAPVS	12758
	SNGYNYL
	D
304	KSS-	12239	WASSRQS	12499	QQYYSTPLT	12759
	QSVLSSSY
	NKNYLA
305	KSS-	12240	WASVRES	12500	QQYYSTPIT	12760
	QSVSSSSY
	NKNYLA
306	KSTQNVLS	12241	WASTRES	12501	QQYYSTPFT	12761
	SSNNN-
	SYLA
307	QASQDIG	12242	AASSLQS	12502	QQTYNTPLT	12762
	NYLN
308	QASQDIS	12243	EASTLQS	12503	QQSYSTPFT	12763
	NYLN
309	QASQDIST	12244	RASTLES	12504	QQSYSIPLT	12764
	WLA
310	RASQNIN-	12245	AASRLQS	12505	QQSYSAPVT	12765
	NYLN
311	RASQNINT	12246	AASSLQS	12506	QQAYSFPFT	12766
	WLA
312	RASQRIGN	12247	AASSLQS	12507	QQSYSTPLT	12767
	YLN
313	RASQSIST	12248	AASTLQS	12508	QQSYRTVT	12768
	YLN
314	RASQSVG	12249	GASTRAT	12509	QQYDSSSQT	12769
	SYLA
315	RASRSVST	12250	GASTRAT	12510	QQYDGSPYT	12770
	YLA
316	RSSQSLLH	12251	DASNLET	12511	MQALQTPPA	12771
	SNGYNYL
	D
317	KSS-	12252	WASTRES	12512	QQYYSAPPT	12772
	QSVLSSSY
	NKNFLA
318	KSS-	12253	WASTRES	12513	QQYYSDPIT	12773
	QSVLSSSY
	NKNFLA
319	KSS-	12254	WASARES	12514	QQYYSIPIA	12774
	QSVLSSSY
	NKNYLA
320	KSS-	12255	WASTRDS	12515	QQYYSIPYT	12775
	QSVLSSSY
	NKNYLA
321	KSS-	12256	WASTRAS	12516	QQYYTTPPT	12776
	QSVLSTSY
	NKNYLA
322	KSS-	12257	WASTRQS	12517	QQYYSTPYT	12777
	QSVLSTSY
	NRNFLA
323	KSS-	12258	WASTRES	12518	QQYYSTPLT	12778
	QSVLYSSN
	NKNYLA
324	QASQDIS	12259	AASSLQS	12519	QQSYSTPT	12779
	NYLN
325	QASQDIS	12260	GASTLQS	12520	QEADSFPLT	12780
	NYLN
326	RASQGIRN	12261	DASSLHS	12521	QQAYSFPWT	12781
	DLG
327	RASQGISN	12262	KASSLES	12522	QQSYNTPFT	12782
	YLA
262	RASQGISN	12263	KASSLES	12523	QQSYNTPFT	12783
	YLA
328	RASQSINR	12264	SASNLQS	12524	QQSYNTPLT	12784
	WLA
329	RASQSINT	12265	AASSLQS	12525	QQANSFPFT	12785
	WLA
330	RASQSIRT-	12266	DASSLET	12526	QQLNSYPLT	12786
	WLA
331	RASQSIRT	12267	AASTLQS	12527	QQSYSAPLT	12787
	YLN
332	RASQSIST	12268	AASSLHS	12528	QQSYSTPLT	12788
	YLN
333	RASQSIT-	12269	AASTLQS	12529	QQSYSTPLT	12789
	TYLN
334	RSSQSLLH	12270	AASSLQS	12530	MQARQTPLT	12790
	SNGYNYL
	D
335	RSSQSLLH	12271	GASSLQS	12531	MQTLQTPFT	12791
	SNGYNYL
	D
336	RSSQSLLH	12272	LGSDRAS	12532	MQALQTPLT	12792
	SNGYNYL
	D
337	KSSQTVF-	12273	WASTRES	12533	QQYYSTPLT	12793
	STSYN-
	KNYLA
338	KTSQSVF-	12274	WASTRES	12534	QQYYSSPPT	12794
	STSYN-
	RDYLA
339	RASQSISS	12275	DASTLQS	12535	QQSYSTPFT	12795
	WLA
340	RASQSIS-	12276	DASNLKT	12536	QQSYSFPT	12796
	SYLN
341	RASQSVSS	12277	DTSSRAT	12537	QQYYDTPYT	12797
	YLA
342	KSS-	12278	LASTREP	12538	QQYYSTPPT	12798
	QSVLYSSN
	NKNYLA
343	KSS-	12279	WASTRES	12539	QQYYSTPLT	12799
	QSVLSSSY
	NKNYVA
344	QASQDIS	12280	AAASLQS	12540	QQTYSTPWT	12800
	NYLN
345	RASQDIN-	12281	AASSLQS	12541	QQSSSFPLT	12801
	TYLA
346	QASQDIS	12282	AASSLQS	12542	QQLYNFPYT	12802
	NYLN
347	RASQSISR	12283	GASTRES	12543	QQSYNTPLT	12803
	YLA
348	RASQTLSG	12284	GASTLQG	12544	QQYYSYPPT	12804
	WLA
349	FASQDI-	12285	EASNLET	12545	QQSYSTPLT	12805
	INYLN
350	RASQSIS-	12286	DVFNLGT	12546	QQSYSSPFT	12806
	SYLN
351	QASQDIS	12287	MASNLES	12547	QQTNSFPLT	12807
	NYLN
352	RASQSIS-	12288	DASNLET	12548	QQSYSTPLT	12808
	SYLN
353	RSSQSLLH	12289	LGSNRAS	12549	MQALQSPWT	12809
	SNGYNYL
	D
354	KSS-	12290	WASTRES	12550	QQYYSSPLT	12810
	QSVLYSSN
	NKNYLA
355	RSSQSLLH	12291	LGSNRAS	12551	MQALQTPPS	12811
	SNGYNYL
	D
356	RAS-	12292	KASRLES	12552	QQSYKTPYT	12812
	ESVST-
	WLA
357	KSS-	12293	WASTRES	12553	QQYFTTPLT	12813
	QSVLYSSN
	NKNYLA
358	RASQSIS-	12294	AASSLQS	12554	QQSYSTPYT	12814
	SYLN
359	KSS-	12295	WASTRAS	12555	QQYYDTPLT	12815
	QSVLSSSY
	NKNYLA
360	RASQSIS-	12296	KASTLES	12556	QQNDSIPIT	12816
	SYLN
361	RASQSISR	12297	DASNLET	12557	LQDYSYPLT	12817
	WLA
362	KTSQSVF-	12298	WASTRAA	12558	QQYYYTST	12818
	STSYN-
	RDYLA
363	RASQSIN-	12299	AASSLQS	12559	QQANSFPPT	12819
	RYLN
364	RASQGISN	12300	SASNLQS	12560	QQSYSTPLT	12820
	YLA
259	RASQGISN	12301	SASNLQS	12561	QQSYSTPLT	12821
	YLA
365	RASQSIDS	12302	KASTLES	12562	QQSYSAPLT	12822
	YLN
366	RASQDIST	12303	DASNLET	12563	QQVNSDPYT	12823
	WLA
367	QASQDIS	12304	AASTLES	12564	QQGDSLPLT	12824
	NYLN
368	RASQGISN	12305	AASSLQS	12565	QQSDSFPYT	12825
	YLA
369	RASQSVST	12306	GASTRAT	12566	QQHDSYPLT	12826
	YLA
370	RASQGIRN	12307	AASSLQS	12567	QQANSFPPT	12827
	DLG
371	RAS-	12308	KASNLES	12568	QQTDSTFIT	12828
	ESISTYLN
372	RASRNIHD	12309	AASTLQT	12569	QQTYSTPPT	12829
	YLN
373	RASQSND	12310	KASTLES	12570	QQSYSSPLT	12830
	SYLN
374	RASQSISD	12311	AASTLQS	12571	QQSYSSPYT	12831
	FLN
375	QASQDIS	12312	AASSLQS	12572	QQANRFPLT	12832
	NYLN
376	QASQDIS	12313	KASNLQS	12573	QQSYNFPAT	12833
	NYLN
377	RSSQSLLH	12314	LGSNRAS	12574	MQGTHWPET	12834
	SNGYNYL
	D
378	RASQSIS-	12315	DASNLET	12575	QQSYSTPLT	12835
	SYLN
379	RASQGISD	12316	DASNLET	12576	QQSYILPLT	12836
	YLA
380	RASQDIN	12317	AASSLQS	12577	QQSYSAPYT	12837
	DFLA
381	RASQSISN	12318	AASKLES	12578	QQSYSSPWT	12838
	WLA
382	RASQGIDS	12319	AASTLES	12579	QQAYSFPLT	12839
	WLA
383	RASQNIGT	12320	RASSLES	12580	QQAYSFPWT	12840
	WLA
384	RASQNIN	12321	KASTLQS	12581	QQADSFPPT	12841
	NWLA
385	RASQDIS-	12322	AASTLQS	12582	QQLNRYPIT	12842
	SYLA
386	RASQDISN	12323	AASILHS	12583	QQYDSSFIT	12843
	YLA

TABLE 23
CDRs using the Chothia Numbering Scheme
Table 5-Chothia CDR Sequences

Binder
Name

HCDR1

HCDR2

HCDR3

		SEQ ID		SEQ ID		SEQ ID
	Sequence	NO:	Sequence	NO:	Sequence	NO:
109	GYTFSSY	3077	LPGSGS	3591	ARRAYGYDGGFDY	4105
110	GYTFSSY	3078	LPGSGS	3592	ARRAYGYDEGFDY	4106
111	GYTFSSY	3079	LPGSDS	3593	ARRAYGYDEGFDY	4107
112	AYTFSIY	3080	LPGSGS	3594	ARRAYGYDGGFDY	4108
1	GYTFSSY	3081	FPGSGH	3595	ARRGYGYDEGFDY	4109
113	GYTFSSY	3082	LPGSGS	3596	ARRGYGYDEGFDY	4110
114	GYTFSSY	3083	LPGSGS	3597	ARRGYGYDEGFDY	4111
115	GYTFSNY	3084	LPGSGS	3598	ARRGYGYDEGFDY	4112
23	GYTFSSY	3085	LPGSGS	3599	ARRGYGYDEGFDY	4113
116	GYTFSSY	3086	LPGSGY	3600	ARRGYGYDEGFDY	4114
117	GYTFSSY	3087	LPGSGS	3601	ARRAYGYDEGFDY	4115
2	GYTLSSY	3088	LPGSGS	3602	ARRGYGYDEGFDY	4116
118	GYTFSSY	3089	LPGSGS	3603	ARRAYGYDEGFDY	4117
119	GYTFSSY	3090	SPGSGS	3604	ARRGYGYDEGFDY	4118
120	GYTFGTY	3091	LPGSGT	3605	ARRAYGYDAGFDY	4119
121	GYTFSSY	3092	LPGSGS	3606	ARRGYGYDEGFDY	4120
122	GYTFSSY	3093	LPGSGR	3607	ARRGYGYDEGFDY	4121
123	GYTFSSY	3094	LPGSGR	3608	ARRGYGYDEGFDY	4122
38	GYTFSSY	3095	LPGSGS	3609	ARRAYGYDEGFDY	4123
39	GYTFSSY	3096	LPGSGS	3610	ARRAYGYDEGFDY	4124
40	GYTFSSY	3097	LPGSGR	3611	ARRGYGYDEGFDY	4125
41	GYTFSSY	3098	LPGSGS	3612	ARRAYGYDEGFDY	4126
42	GYTFSSY	3099	LPGSGR	3613	ARRGYGYDEGFDY	4127
43	GYTFSSY	3100	LPGSGS	3614	ARRAYGYDGGFDY	4128
44	GYTFSSY	3101	LPGSDS	3615	ARRAYGYDEGFDY	4129
45	AYTFSIY	3102	LPGSGS	3616	ARRAYGYDGGFDY	4130
46	GYTFSSY	3103	FPGSGH	3617	ARRGYGYDEGFDY	4131
47	GYTFSNY	3104	LPGSGS	3618	ARRGYGYDEGFDY	4132
47	GYTFSNY	3104	LPGSGS	3618	ARRGYGYDEGFDY	4132
48	GYTFSSY	3105	LPGSGS	3619	ARRGYGYDEGFDY	4133
48	GYTFSSY	3105	LPGSGS	3619	ARRGYGYDEGFDY	4133
49	GYTFSSY	3106	LPGSGY	3620	ARRGYGYDEGFDY	4134
50	GYTLSSY	3107	LPGSGS	3621	ARRGYGYDEGFDY	4135
51	GYTFSSY	3108	SPGSGS	3622	ARRGYGYDEGFDY	4136
52	GYTFGTY	3109	LPGSGT	3623	ARRAYGYDAGFDY	4137
53	GYTFSSY	3110	LPGSGS	3624	ARRGYGYDEGFDY	4138
54	GYTFSSY	3111	LPGSGR	3625	ARRGYGYDEGFDY	4139
55	GYTFSNY	3112	LPGSGS	3626	ARRGYGYDEGFDY	4140
56	GYTFSSY	3113	LPGSGS	3627	ARRGYGYDEGFDY	4141
3	GYSFTGY	3114	SSYNGA	3628	ARGRYGEYFDY	4142
4	GYSFTGY	3115	SSYNGV	3629	ARGRYGDYFDY	4143
5	GYSFTGY	3116	SSYNGV	3630	ARGRYGDYFDY	4144
6	GYSFTGY	3117	SSYNGV	3631	ARGRYGDYFDY	4145
7	GYSFTGY	3118	SSYNGA	3632	ARGRYGDYFDY	4146
8	GYSFTGY	3119	SSYNGV	3633	ARGRYGDYFDY	4147
9	GYSFTGY	3120	SSYNGV	3634	ARGRYGDYFDY	4148
10	GYSFTGY	3121	SSYNGV	3635	ARGRYGDYFDY	4149
11	GYSFTGY	3122	SSYNGV	3636	ARGRYGDYFDY	4150
12	GYSFTGF	3123	SSYNGA	3637	ARGRYGDYFDY	4151
13	GYSFTGY	3124	SSYNGA	3638	ARGRYGDYFDY	4152
57	GYSFTGY	3125	SSYNGV	3639	ARGRYGDYFDY	4153
58	GYSFTGY	3126	SSYNGA	3640	ARGRYGEYFDY	4154
124	GFSLSSY	3127	WRGGS	3641	AKNLYGHYVMDY	4155
125	GFSVTSY	3128	WRGGS	3642	AKNLYGHYVMDY	4156
126	GFSLTSY	3129	WRGGS	3643	AKNLYGHYVMDY	4157
127	GFSLTRY	3130	WRGGS	3644	AKNLYGHYVMDY	4158
128	GFSVTTY	3131	WRGGS	3645	AKNLYGHYVMDY	4159
129	GFSVTSY	3132	WRGGS	3646	AKNLYGHYVMDY	4160
130	GFSLTRY	3133	WRGGS	3647	AKNLYGHYVMDY	4161
59	GFSLSSY	3134	WRGGS	3648	AKNLYGHYVMDY	4162
60	GFSVTSY	3135	WRGGS	3649	AKNLYGHYVMDY	4163
61	GFSLTSY	3136	WRGGS	3650	AKNLYGHYVMDY	4164
62	GFSLTRY	3137	WRGGS	3651	AKNLYGHYVMDY	4165
63	GFSVTTY	3138	WRGGS	3652	AKNLYGHYVMDY	4166
131	GYTFTSY	3139	HPNSGS	3653	ARWGDGYSFAY	4167
132	GYTFTSY	3140	HPNSGS	3654	ARWGDGYSFAY	4168
133	GYTFTTY	3141	HPNSDN	3655	ARWGDGYSFAY	4169
14	GYTFTSY	3142	HPNSGT	3656	ARWGDGYSFAY	4170
134	GYTFTSY	3143	HPNSGN	3657	ARWGDGYSFAY	4171
64	GYTFTSY	3144	HPNSGS	3658	ARWGDGYSFAY	4172
65	GYTFTSY	3145	HPNSGT	3659	ARWGDGYSFAY	4173
135	GYTFTDY	3146	YPGSGS	3660	ARRGERGPWFAY	4174
136	GYTFTDY	3147	YPGSGS	3661	ARRGERGPWFAY	4175
137	GYTFTDY	3148	YPGSGS	3662	ARRGERGPWFAY	4176
138	GYTFTDY	3149	YPGSGS	3663	ARRGERGPWFAY	4177
15	GYTFTDY	3150	YPGSGS	3664	ARRGERGPWFAY	4178
66	GYTFTDY	3151	YPGSGS	3665	ARRGERGPWFAY	4179
67	GYTFTDY	3152	YPGSGS	3666	ARRGERGPWFAY	4180
68	GYTFTDY	3153	YPGSGS	3667	ARRGERGPWFAY	4181
69	GYTFTDY	3154	YPGSGS	3668	ARRGERGPWFAY	4182
24	GYTFTNY	3155	DPSDSE	3669	ATYDVYYRFAY	4183
139	GYTFTNY	3156	DPSDSE	3670	ATYDGYYRFAY	4184
140	GYTFTNY	3157	DPSDSE	3671	ATYDIYYRFAY	4185
16	GYTFTSY	3158	HPNSGS	3672	ARPGGYGFVY	4186
141	GYTFTSY	3159	HPNSDS	3673	ARPGGYGFAD	4187
142	GYTFTTY	3160	HPNSGS	3674	ARPGGYGFTY	4188
143	GYTFTSY	3161	HPNSGS	3675	ARPGGYGFAY	4189
70	GYTFTSY	3162	HPNSGS	3676	ARPGGYGFAY	4190
25	GYTFTSY	3163	YPSDSY	3677	TRGNYIDY	4191
144	GYTFTSY	3164	YPSDSY	3678	TRGNYIDY	4192
145	GYTFTDY	3165	YPSDSY	3679	TRGNYIDY	4193
146	GYTFTDY	3166	YPGSGS	3680	ARPGDLGFAY	4194
147	GYTFTDY	3167	YPGSGS	3681	ARPGDLGFAY	4195
148	GYTFTDY	3168	YPGSGS	3682	ARPGDLGFAY	4196
71	GYTFTDY	3169	YPGSGS	3683	ARPGDLGFAY	4197
72	GYTFTDY	3170	YPGSGS	3684	ARPGDLGFAY	4198
73	GYTFTDY	3171	YPGSGS	3685	ARPGDLGFAY	4199
74	GYTFTDY	3172	YPGSGS	3686	ARPGDLGFAY	4200
74	GYTFTDY	3172	YPGSGS	3686	ARPGDLGFAY	4200
75	GYTFTDY	3173	YPGSGS	3687	ARPGDLGFAY	4201
75	GYTFTDY	3173	YPGSGS	3687	ARPGDLGFAY	4201
76	GYTFTDY	3174	YPGSGS	3688	ARPGDLGFAY	4202
149	GFSLTNY	3175	WAGGI	3689	ARGDGYDDGYAMDY	4203
150	GFSLTSY	3176	WAGGI	3690	ARGDGYDDGYAMDY	4204
26	GFSLTSY	3177	WAGGT	3691	ARGDGYDDGYAMDY	4205
77	GFSLTNY	3178	WAGGI	3692	ARGDGYDDGYAMDY	4206
78	GFSLTSY	3179	WAGGI	3693	ARGDGYDDGYAMDY	4207
79	GFSLTSY	3180	WAGGT	3694	ARGDGYDDGYAMDY	4208
151	GYSFTSY	3181	DPSDSE	3695	ARTRNY	4209
152	GYSFTSY	3182	DPSDSE	3696	ARTRNY	4210
153	GYSFTSY	3183	DPSDSE	3697	ARTRNY	4211
154	GFNIKDY	3184	DPENGD	3698	NAPLLRYSSAMDY	4212
155	GFNIKDY	3185	DPENGD	3699	NAPLLRYSSSMDY	4213
156	GFNIKDY	3186	DPENGD	3700	NVALLRYSSAMDY	4214
80	GFNIKDY	3187	DPENGD	3701	NAPLLRYSSAMDY	4215
81	GFNIKDY	3188	DPENGD	3702	NAPLLRYSSSMDY	4216
82	GFNIKDY	3189	DPENGD	3703	NVALLRYSSAMDY	4217
17	GFNIKDT	3190	DPANGN	3704	ARGPDDGYFYYYSMDY	4218
157	GYTFSNY	3191	NPSNGD	3705	TSYYTHEAYYYAMDC	4219
27	GSTFTTY	3192	NPSNGG	3706	TSYYTHETYYYAMDY	4220
158	GFNIKDY	3193	DPEDGD	3707	TPYSIYDAMDY	4221
159	GYTFTDY	3194	YPGSGS	3708	ARRGERGPWFAY	4222
83	GYTFTDY	3195	YPGSGS	3709	ARRGERGPWFAY	4223
160	GYSFTDY	3196	STYYGD	3710	ARQMDYDYTYYYAMDY	4224
28	GYTFTSY	3197	DPSDSY	3711	ARAEYGYGNYPWFAY	4225
84	GYTFTSY	3198	DPSDSY	3712	ARAEYGYGNYPWFAY	4226
29	GYTFTSY	3199	HPSDSD	3713	AIPYYYGGWYFDV	4227
161	GYTFTDY	3200	YPGSGS	3714	ARMDGPWFAY	4228
30	GFTFSSY	3201	SSGGSY	3715	ARLYDAHWDYFDY	4229
162	GISLSTSGM	3202	WNND	3716	AWRPYYRYDSFAY	4230
18	GYTFTNY	3203	NTYTGE	3717	ARKYYDYEFAY	4231
85	GYTFTNY	3204	NTYTGE	3718	ARKYYDYEFAY	4232
163	GYTFTDY	3205	DPETGG	3719	TRLGDYDVMDY	4233
86	GYTFTDY	3206	DPETGG	3720	TRLGDYDVMDY	4234
164	GYTFTSY	3207	DPSDSY	3721	ARAGRYGSSFDY	4235
165	GFSLSTSGM	3208	YWDDD	3722	AGRPDDYDGAWFPY	4236
31	GYTFTSS	3209	HPNSGN	3723	AIYYDYDAYYFDY	4237
87	GYTFTSS	3210	HPNSGN	3724	AIYYDYDAYYFDY	4238
32	GYTFTSY	3211	HPNSGS	3725	ANPYYGYDVGY	4239
166	GYTFTDY	3212	YPGSGS	3726	AREEKIYFDY	4240
88	GYTFTDY	3213	YPGSGS	3727	AREEKIYFDY	4241
167	GYTFTSY	3214	HPNSGS	3728	ARYDGYWFDY	4242
168	GYTFTSY	3215	YPGNSD	3729	TSLITTAYYFDY	4243
89	GYTFTSY	3216	YPGNSD	3730	TSLITTAYYFDY	4244
169	GYTFTSY	3217	HPNSGS	3731	APETGDYGSSYVWYFDV	4245
170	GYTFTDY	3218	YPGSGS	3732	ARGKVTRFAY	4246
171	GFTFSSY	3219	SDGGSY	3733	ARDQDSNWEYFDY	4247
172	GYTFTDY	3220	NTETGE	3734	ARESWDRAMDY	4248
19	GFTFSSY	3221	SSGGSY	3735	ARHEEANWAWFAY	4249
90	GFTFSSY	3222	SSGGSY	3736	ARHEEANWAWFAY	4250
173	GYSFTNY	3223	DPSDSE	3737	AIPYYAMDY	4251
91	GYSFTNY	3224	DPSDSE	3738	AIPYYAMDY	4252
174	GYTFTSS	3225	HPNSGN	3739	ATYYGNYVWYFDV	4253
92	GYTFTSS	3226	HPNSGN	3740	ATYYGNYVWYFDV	4254
175	GYTFTSY	3227	HPNSGS	3741	ASYGSSYWYFDV	4255
93	GYTFTSY	3228	HPNSGS	3742	ASYGSSYWYFDV	4256
20	GFSLTSY	3229	WSGGS	3743	ASYYGSSRSYWYLDV	4257
94	GFSLTSY	3230	WSGGS	3744	ASYYGSSRSYWYLDV	4258
176	GYTFTSY	3231	YSGNGD	3745	ARDYYGSSHLWYFDV	4259
177	GFSLSTSGM	3232	YWDDD	3746	ARRAHYDYGWYFDV	4260
178	GYTFTSY	3233	HPNSGS	3747	AGYDYDWYFDV	4261
33	GFTFSSY	3234	SSGGSY	3748	TRHDDSSYDWFAY	4262
179	GFTFSSY	3235	SSGGSY	3749	ARHEDSNYHYFDY	4263
34	GYTFTNY	3236	HPNSGT	3750	ARFGDGYHFDY	4264
180	GFTFSSY	3237	SSGGSY	3751	ARQNDSSWAWFAY	4265
95	GFTFSSY	3238	SSGGSY	3752	ARQNDSSWAWFAY	4266
181	GYTFTSY	3239	HPNSGS	3753	ALPYSNYGWYFDV	4267
96	GYTFTSY	3240	HPNSGS	3754	ALPYSNYGWYFDV	4268
182	GYTFTSY	3241	DPSDSE	3755	ARDYYGSYWYFDV	4269
97	GYTFTSY	3242	DPSDSE	3756	ARDYYGSYWYFDV	4270
183	GFNIKDY	3243	DPEDGE	3757	AAYGNSAWFAY	4271
98	GFNIKDY	3244	DPEDGE	3758	AAYGNSAWFAY	4272
35	GYTFTNY	3245	NTNTGE	3759	ARWYPYFDY	4273
99	GYTFTNY	3246	NTNTGE	3760	ARWYPYFDY	4274
100	GYTFTNY	3247	NTNTGE	3761	ARWYPYFDY	4275
36	GYTFTSY	3248	NPSSGY	3762	ARSDGSSGNWYFDV	4276
101	GYTFTSY	3249	NPSSGY	3763	ARSDGSSGNWYFDV	4277
184	GFSLTSY	3250	WAGGS	3764	AREGGYTGYFDV	4278
102	GFSLTSY	3251	WAGGS	3765	AREGGYTGYFDV	4279
185	GYTFTSY	3252	DPSDSE	3766	AYSNYVPYYAMDY	4280
103	GYTFTSY	3253	DPSDSE	3767	AYSNYVPYYAMDY	4281
186	GYTFTDY	3254	YPGSGS	3768	ARRGFDY	4282
21	GFTFSSY	3255	SSGGSY	3769	ARHNYSNWDWFAY	4283
187	GYTFTSY	3256	HPNSGS	3770	ARDYYGSGYGYYFDY	4284
188	GYTFTSY	3257	HPNSGS	3771	ARDYYGSSYGWYFDV	4285
189	GYTFTSY	3258	HPNSGS	3772	ARDYYGSSYGWYFDV	4286
190	GYTFTSY	3259	HPNSGS	3773	ASDYYGSSYGWYFDV	4287
191	GYTFTSY	3260	HPNSGS	3774	ARDYYGSSYGWYFDV	4288
192	GYTFTSY	3261	HPNSGS	3775	TRDYYGSGYGWYFDV	4289
193	GYTFTNY	3262	DPSDSE	3776	ATYDGYYRFAY	4290
194	GYTFTNY	3263	DPSDSE	3777	ATYDVYYRFAY	4291
195	GYTFTSY	3264	HPNSGS	3778	ARDYGNYDYAMDY	4292
104	GYTFTSY	3265	HPNSGS	3779	ARDYGNYDYAMDY	4293
37	GYTFTSY	3266	HPNSGS	3780	ARDYGNYDYAMDY	4294
196	GYTFTSY	3267	HPNSGS	3781	ARDYGNYDYAMDY	4295
197	GFTFSSY	3268	SSGGSY	3782	ASQLTGTWYYFDY	4296
198	GFTFSSY	3269	SSGGSY	3783	ASQLTGTWYYFDY	4297
199	GFTFSSY	3270	SSGGSY	3784	ASQLTGTWYYFDY	4298
22	GFNIKDT	3271	DPANGN	3785	ARGPDDGYFYYYSMDY	4299
200	GFTFSNY	3272	NSNGGS	3786	ARQEGIGYAMDY	4300
201	GYTFTEY	3273	YPNNGG	3787	ARGGWLLGY	4301
202	GFSLTSY	3274	WSGGS	3788	ARDGGIRGAMDY	4302
203	GYTFSSY	3275	LPGSGS	3789	ARRGYGYDEGFDY	4303
204	GYTFTDY	3276	DPETGG	3790	TRNYDYAMDY	4304
205	GFTFSSY	3277	NSNGGS	3791	ARQEGIGYALDY	4305
206	GFTFSSY	3278	SSGGS	3792	AREREWGVYYGSSLDY	4306
207	GFNIKDT	3279	DPANGN	3793	ARSDGNYD	4307
208	GFTFSNY	3280	NSNGGS	3794	ARQEGIGYGMDY	4308
209	GFTFNTY	3281	RSKSDNYA	3795	VRHDGVVGFDV	4309
210	GYSITSGY	3282	SYDGS	3796	ARGGGRG	4310
211	GYTFTDY	3283	NTETGE	3797	ARDYYDYYYAMDY	4311
212	GYTFTDY	3284	NTETGE	3798	ARESWDRAMDY	4312
213	GYTFTNY	3285	DPYDSE	3799	ARIYSDYDGAWFAY	4313
214	GYTFTDY	3286	NPYNGG	3800	ARGTVGFAY	4314
215	GFTFSSY	3287	SSGGS	3801	AREREWGVFYGSSLDY	4315
216	GFTFSSY	3288	SSGGSY	3802	ARHDDSSYGYFDY	4316
217	GFTFSNY	3289	SSGGT	3803	ARTMPDV	4317
218	GFSLTSY	3290	WAGGS	3804	ARDTDGYYWAMDY	4318
219	GYSITSDH	3291	SYSGS	3805	ARKWGDY	4319
220	GYTFTDY	3292	DPETGG	3806	TRNYDYALDY	4320
221	GYSITSGY	3293	SYDGS	3807	ARGGGRG	4321
222	GFTFSNY	3294	NSNGGS	3808	ARQEEIGYAMDY	4322
223	GFNIKDY	3295	DPETDN	3809	ARSGNMGFTY	4323
105	GFNIKDY	3296	DPETDN	3810	ARSGNMGFTY	4324
224	GFTFSSY	3297	SSGGSY	3811	ASQGGSSWGAMDY	4325
106	GFTFSSY	3298	SSGGSY	3812	ASQGGSSWGAMDY	4326
225	GFTFSSY	3299	SNGGSY	3813	ARHEITTRFAY	4327
226	GYSITSGY	3300	SYDGS	3814	AREAGYFDY	4328
227	GFSFNTY	3301	RSKSNNYA	3815	VRQYGYDFDY	4329
228	GFTFSSY	3302	SSGGSY	3816	ARHKGVNWDYFDY	4330
229	GYTFTDY	3303	DPETGG	3817	TRGDGNYDSWYFDV	4331
230	GFTFSSY	3304	SSGGSY	3818	ARLPVTTVVFDY	4332
231	GFTFSSY	3305	SSGGSY	3819	ARRPVVVPFDY	4333
232	GFSLTSY	3306	WSGGS	3820	ARGWDADYFDY	4334
233	GYTFTNY	3307	HPNSGS	3821	TRYDYDDY	4335
234	GYTFTDY	3308	NPNNGG	3822	ARSELGLYAMDY	4336
235	GYTFTGY	3309	LPGSGS	3823	ARGRIHYFDY	4337
236	GYTFTGY	3310	LPGSGS	3824	ARGRIHYFDY	4338
237	GFSLTSY	3311	WSGGS	3825	ARKGYGYDWYFDV	4339
107	GFSLTSY	3312	WSGGS	3826	ARKGYGYDWYFDV	4340
238	GYTFTSY	3313	DPSDSY	3827	ARSSYYYYAMDY	4341
108	GYTFTSY	3314	DPSDSY	3828	ARSSYYYYAMDY	4342
239	GYSITSGY	3315	SYDGS	3829	ARGGGRD	4343
240	GFSLTSY	3316	WSGGS	3830	ARGGDYDSYAMDY	4344
241	GYTFTSY	3317	YPGSGS	3831	ARESVYDGYSWYFDV	4345
242	GYSFTDY	3318	NPNYGT	3832	ASTYDYDDWYFDV	4346
243	GYTFTSY	3319	DPSDSY	3833	ARSGNYLYAMDY	4347
244	GYSFTDY	3320	NPNYGT	3834	AREGTSWYFDV	4348
245	GFSLTSY	3321	WRGGS	3835	AKKGDGYDWYFDV	4349
246	GFSLTSY	3322	WSGGS	3836	AREGNYGSSYDAMDY	4350
247	GYTFTSY	3323	DPSDSY	3837	ARSSNYPYAMDY	4351
248	GFNIKNT	3324	DPANGN	3838	AYYSGLY	4352
249	GYTFTSY	3325	DPSDSE	3839	ARRGQIYYGYSWFAY	4353
250	GYTFTDY	3326	NPNNGG	3840	ARSTVVADWYFDV	4354
251	GYTFTSY	3327	YPRSGN	3841	ARSGSSYGYFDV	4355
252	GFSLTSY	3328	WSGGS	3842	ARKGGYDAYAMDY	4356
253	GYSFTDY	3329	NPNYGT	3843	AREGFITTVVAVDY	4357
254	GYTFTDY	3330	DPETGG	3844	TREGNYDAMDY	4358
255	GYTFTSY	3331	DPSDSY	3845	ARWDYYGVDY	4359
256	GFTFSGY	3332	SPGGGS	3846	ASSLTATHTYEYDY	4360

LCDR1

LCDR2

LCDR3

		SEQ ID		SEQ ID		SEQ ID
	Sequence	NO:	Sequence	NO:	Sequence	NO:
109	KASQDIN-	5644	KTLIYRANRLVD	7505	LHYDEFPPT	6664
	SYLS
110	KASQDIN-	5645	KTLIYRANRLVD	7506	LQYDEFPPT	6665
	SYLN
111	KASQDIN-	5646	KTLIYRANRLVD	7507	LQYDEFPPT	6666
	SYLS
112	KASQDIN-	5647	KTLIYRANRLVD	7508	LQYDEFPPT	6667
	SYLS
1	KASQDIN-	5648	KTLIYRANRLVD	7509	LQYDEFPPT	6668
	SYLS
113	KASQDIN-	5649	KTLIYRANRLVD	7510	PQYVESPPT	6669
	SYLS
114	KASQDIN-	5650	KTLIYRANRLVD	7511	LQYDEFPPT	6670
	SYLS
115	KASQDIN-	5651	KTLIYRANRLVD	7512	LQYDEFPPT	6671
	SYLS
23	KASQDIN-	5652	KTLIYRANRLVD	7513	LQYDEFPPT	6672
	SYLS
116	KASQDIN-	5653	KTLIYRANRLVD	7514	LQYDEFPPT	6673
	SYLS
117	KASQDIN-	5654	KTLIYRANRLVD	7515	LQYDEFPLT	6674
	SYLS
2	KASQDIN-	5655	KTLIYRANRLVD	7516	LQYDEFPPT	6675
	SYLS
118	KASQDIN-	5656	QTLLYRANRLVD	7517	LQYDEFPPT	6676
	GYLS
119	KASQDIN-	5657	KTLIYRANRLVD	7518	LQYDEFPPT	6677
	SYLS
120	KASQDIN-	5658	KTLIYRANRLVD	7519	LQYDEFPPT	6678
	SYLS
121	KASQDIN-	5659	KTLIYRANRLVD	7520	LQYDEFPPT	6679
	SYLN
122	KASQDIN-	5660	KTLIYRANRLVD	7521	LQYDEFPPT	6680
	SYLS
123	KASQDIN-	5661	KTLIYRAKRLVD	7522	LQYDEFPPT	6681
	SYLS
38	KASQDIN-	7174	KTLIYRANRLVD	7523	LQYDEFPLT	6682
	SYLS
39	KASQDIN-	7175	QTLLYRANRLVD	7524	LQYDEFPPT	6683
	GYLS
40	KASQDIN-	7176	KTLIYRAKRLVD	7525	LQYDEFPPT	6684
	SYLS
41	KASQDIN-	7177	QTLLYRANRLVD	7526	LQYDEFPPT	6685
	GYLS
42	KASQDIN-	7178	KTLIYRAKRLVD	7527	LQYDEFPPT	6686
	SYLS
43	KASQDIN-	7179	KTLIYRANRLVD	7528	LHYDEFPPT	6687
	SYLS
44	KASQDIN-	7180	KTLIYRANRLVD	7529	LQYDEFPPT	6688
	SYLS
45	KASQDIN-	7181	KTLIYRANRLVD	7530	LQYDEFPPT	6689
	SYLS
46	KASQDIN-	7182	KTLIYRANRLVD	7531	LQYDEFPPT	6690
	SYLS
47	KASQDIN-	7183	KTLIYRANRLVD	7532	LQYDEFPPT	6691
	SYLS
48	KASQDIN-	7184	KTLIYRANRLVD	7533	LQYDEFPPT	6692
	SYLS
49	KASQDIN-	7185	KTLIYRANRLVD	7534	LQYDEFPPT	6693
	SYLS
50	KASQDIN-	7186	KTLIYRANRLVD	7535	LQYDEFPPT	6694
	SYLS
51	KASQDIN-	7187	KTLIYRANRLVD	7536	LQYDEFPPT	6695
	SYLS
52	KASQDIN-	7188	KTLIYRANRLVD	7537	LQYDEFPPT	6696
	SYLS
53	KASQDIN-	7189	KTLIYRANRLVD	7538	LQYDEFPPT	6697
	SYLN
54	KASQDIN-	7190	KTLIYRANRLVD	7539	LQYDEFPPT	6698
	SYLS
55	KASQDIN-	7191	KTLIYRANRLVD	7540	LQYDEFPPT	6699
	SYLS
56	KASQDIN-	7192	KTLIYRANRLVD	7541	LQYDEFPPT	6700
	SYLS
3	RASENIYS	5681	QLLVFAATYLAD	7542	QHFWGTPWT	6701
	NLA
4	RASENIYS	5682	QLLVYAATNLAD	7543	QHFWGTPWT	6702
	NLA
5	RASENIYS	5683	QVLVYAATNLAD	7544	QHFWGSPWT	6703
	NLA
6	RASENIYS	5684	RLLVYAATNLAD	7545	QHFWGTPWT	6704
	NLA
7	RASENIYS	5685	QLLVYAATNLAD	7546	QHFWGTPWT	6705
	NLA
8	RASENIYS	5686	QVLVYAATNVAD	7547	QHFWGTPWT	6706
	NLA
9	RAS-	5687	QLLVYAATNLAD	7548	QHFWGTPWT	6707
	DNIYSNLA
10	RASENIYS	5688	RLLVYAATNLAD	7549	QHFWGTPWT	6708
	NLA
11	RASENIYS	5689	QLLVYAATNLAD	7550	QHFWGTPWT	6709
	NLA
12	RASENIYS	5690	QLLVFAATYLAD	7551	QHFWGTPWT	6710
	NLA
13	RASENIYS	5691	QLLVYAATNLAD	7552	QHFWGSPWT	6711
	NLA
57	RAS-	7193	QLLVYAATNLAD	7553	QHFWGTPWT	6712
	DNIYSNLA
58	RASENIYS	7194	QLLVFAATYLAD	7554	QHFWGTPWT	6713
	NLA
124	KASQDIN-	5694	KTLIYRANRLVD	7555	LQYDEFPPT	6714
	SYLS
125	KASEN-	5695	KLLIYGASNRYT	7556	GQSYSYPFT	6715
	VVTYVS
126	KASEN-	5696	KLLIYGASNRYT	7557	GQSYSYPFT	6716
	VVTYVS
127	KASEN-	5697	KLLIYGASNRYT	7558	GQSYSYPFT	6717
	VVTYVS
128	KASEN-	5698	KLLIYGASNRYT	7559	GQSYSYPFT	6718
	VVTYVS
129	KASEN-	5699	KLLIYGASNRYT	7560	GQSYSYLIHVR	7761
	VVTYVS
130	KASEN-	5700	KLLIYGASNRYT	7561	GQSYSYLIHVR	7762
	VVTYVS
59	KASQDIN-	7195	KTLIYRANRLVD	7562	LQYDEFPPT	6721
	SYLS
60	KASEN-	7196	KLLIYGASNRYT	7563	GQSYSYPFT	6722
	VVTYVS
61	KASEN-	7197	KLLIYGASNRYT	7564	GQSYSYPFT	6723
	VVTYVS
62	KASEN-	7198	KLLIYGASNRYT	7565	GQSYSYPFT	6724
	VVTYVS
63	KASEN-	7199	KLLIYGASNRYT	7566	GQSYSYPFT	6725
	VVTYVS
131	SASSSVSY	5706	KRWIYDTSKLAS	7567	QQWSSNPLYT	7763
	MH
132	SASSSVSY	5707	KRWIYDTSKLAS	7568	QQWSSNPHVHV	7764
	MH
133	SASSSVSY	5708	KRWIYDTSKLAS	7569	QQWSSNPLYT	7765
	MH
14	SASSSVSY	5709	KRWIYDTSKLAS	7570	QQWSSNPLYT	7766
	MH
134	SASSSVSY	5710	KRWIYDTSKLAS	7571	QQWSSNPLYT	7767
	MH
64	SASSSVSY	7200	KRWIYDTSKLAS	7572	QQWSSNPLY	6731
	MH
65	SASSSVSY	7201	KRWIYDTSKLAS	7573	QQWSSNPLY	6732
	MH
135	KASQSVD	5713	KLLIYAASNLES	7574	QQSNEDPLT	6733
	YD-
	GDSYMN
136	KASQSVD	5714	KLLIYAASNLES	7575	QQSNEDPLT	6734
	YD-
	GDSYMN
137	KASQSVD	5715	QLLIYAASNLQS	7576	QQSNEDPLT	6735
	YD-
	GDSYMN
138	KASQSVD	5716	KLLIYAASNLES	7577	QQSNEDPLT	6736
	YD-
	GDSYMN
15	KASQSVD	5717	KLLIYAASNLES	7578	QQSNEDPLT	6737
	YD-
	GDSYMN
66	KASQSVD	7202	KLLIYAASNLES	7579	QQSNEDPLT	6738
	YD-
	GDSYMN
67	KASQSVD	7203	KLLIYAASNLES	7580	QQSNEDPLT	6739
	YD-
	GDSYMN
68	KASQSVD	7204	QLLIYAASNLQS	7581	QQSNEDPLT	6740
	YD-
	GDSYMN
69	KASQSVD	7205	KLLIYAASNLES	7582	QQSNEDPLT	6741
	YD-
	GDSYMN
24	KASQDINK	5722	SLLIHYTSTLQP	7583	LQYDNLMYT	6742
	YIA
139	KASQDINK	5723	RLLIHYTSTLQP	7584	LQYDILMYT	6743
	YIA
140	KASQDINK	5724	RLLIHYTSTLQP	7585	LQYDILMYT	6744
	YIA
16	QATQDIV-	5725	SFLIYYATELAE	7586	LQFYEFPLT	6745
	KNLN
141	QATQDIV-	5726	SFLIYYATELAE	7587	LQFYEFPLT	6746
	KNLN
142	QATQDIV-	5727	SFLIYYATELAE	7588	LQFYEFPLT	6747
	KNLN
143	QATQDIV-	5728	SFLIYYATELAE	7589	LQFYEFPLT	6748
	KNLN
70	QATQDIV-	7206	SFLIYYATELAE	7590	LQFYEFPLT	6749
	KNLN
25	RAS-	5730	KLWIYYTSNLAP	7591	QQFTSSHT	7768
	SSVNYMY
144	RAS-	5731	KLWIYYTSNLAP	7592	QQFTSSHT	7769
	SSVNYMY
145	RAS-	5732	KLWIYYTSNLAP	7593	QQFTSSHT	7770
	SSVNYMY
146	KASQSVD	5733	KLLIYAASNLES	7594	QQSNKDPLT	6753
	YD-
	GDSYMN
147	KASQSVD	5734	KLLIYAASNLES	7595	QQSNEDPLT	6754
	YD-
	GDSYMN
148	KASQSVD	5735	KLLIYAASNLES	7596	QQSNKDPFT	6755
	YD-
	GDSYMN
71	KASQSVD	7207	KLLIYAASNLES	7597	QQSNKDPLT	6756
	YD-
	GDSYMN
72	KASQSVD	7208	KLLIYAASNLES	7598	QQSNKDPLT	6757
	YD-
	GDSYMN
73	KASQSVD	7209	KLLIYAASNLES	7599	QQSNEDPLT	6758
	YD-
	GDSYMN
74	KASQSVD	7210	KLLIYAASNLES	7600	QQSNKDPFT	6759
	YD-
	GDSYMN
75	KASQSVD	7211	KLLIYAASNLES	7601	QQSNKDPFT	6760
	YD-
	GDSYMN
76	KASQSVD	7212	KLLIYAASNLES	7602	QQSNKDPFT	6761
	YD-
	GDSYMN
149	RASQSVST	5742	KLLIKYASNLES	7603	QHSWEIPLT	6762
	SSYSYMH
150	RASQSVST	5743	KLLIKYASNLES	7604	QHSWEIPLT	6763
	SSYSYMH
26	RASQSVST	5744	KLLIKYASNLES	7605	QHSWEIPLT	6764
	SSYSYMH
77	RASQSVST	7213	KLLIKYASNLES	7606	QHSWEIPLT	6765
	SSYSYMH
78	RASQSVST	7214	KLLIKYASNLES	7607	QHSWEIPLT	6766
	SSYSYMH
79	RASQSVST	7215	KLLIKYASNLES	7608	QHSWEIPLT	6767
	SSYSYMH
151	RASQDISN	5748	KLLIYSTSRLHS	7609	QQGNTLPWT	6768
	YLN
152	RASQDISN	5749	KLLIYSTSRLHS	7610	QQGNALPWT	6769
	YLN
153	RASQDISN	5750	KLLIYSTSRLHS	7611	QQGNTLPWT	6770
	YLN
154	RSST-	5751	TGLIGGTSNRAP	7612	ALWYSTHYV	6771
	GAVTTSN
	YAN
155	RSST-	5752	TGLIGGTSNRAP	7613	ALWYSTHYV	6772
	GAVTTSN
	YAN
156	RSST-	5753	TGLIGGTSNRAP	7614	ALWYSTHYV	6773
	GAVTTSN
	YAN
80	RSST-	7216	TGLIGGTSNRAP	7615	ALWYSTHYV	6774
	GAVTTSN
	YAN
81	RSST-	7217	TGLIGGTSNRAP	7616	ALWYSTHYV	6775
	GAVTTSN
	YAN
82	RSST-	7218	TGLIGGTSNRAP	7617	ALWYSTHYV	6776
	GAVTTSN
	YAN
17	RASENIYS	5757	QLLVYAATNLAD	7618	QHFWGTPWT	6777
	NLA
157	IT-	5758	KLLISEGNTLRP	7619	LQSDNMPFT	6778
	STDIDDD
	MN
27	MTSIDIDD	5759	KLLISEGNTLRP	7620	LQSDNMPFT	6779
	DMN
158	RSST-	5760	TGLIGGTSNRAP	7621	ALWYSTHY	7771
	GAVTTSN
	YAN
159	KASQSVD	5761	KLLIYAASNLES	7622	QQSNEDPLT	6781
	YD-
	GDSYMN
83	KASQSVD	7219	KLLIYAASNLES	7623	QQSNEDPLT	6782
	YD-
	GDSYMN
160	KSS-	5763	KLLIYWASTRES	7624	QQYYSYPPWT	7772
	QSLLYSTN
	QKNYLA
28	RSST-	5764	TGLIGGTSNRAP	7625	ALWYSTHWV	6784
	GAVTTSN
	YAN
84	RSST-	7220	TGLIGGTSNRAP	7626	ALWYSTHWV	6785
	GAVTTSN
	YAN
29	RSST-	5766	TGLIGGTNNRAP	7627	ALWYSNHL	7773
	GAVTTSN
	YAN
161	KASQSVD	5767	KLLIYAASNLES	7628	QQSNEDPPT	6787
	YD-
	GDSYMN
30	RSST-	5768	TGLIGGTNNRAP	7629	ALWYSNHWV	6788
	GAVTTSN
	YAN
162	RASENIYY	5769	QLLIYNANSLED	7630	KQAYDVPYT	6789
	SLA
18	KSS-	5770	KLLVYFASTRES	7631	QQHYSTPLT	6790
	QSLLNSSN
	QKNYLA
85	KSS-	7221	KLLVYFASTRES	7632	QQHYSTPLT	6791
	QSLLNSSN
	QKNYLA
163	RASQDISN	5772	KLLIYYTSRLHS	7633	QQDNTLPRT	6792
	YLN
86	RASQDISN	7222	KLLIYYTSRLHS	7634	QQDNTLPRT	6793
	YLN
164	RASQDISN	5774	KLLIYYTSRLHS	7635	QQGNTLPWT	6794
	YLN
165	RASENIYS	5775	QLLVYAATNLAD	7636	QHFWGTPWT	6795
	NLA
31	QATQDIV-	5776	SFLIYYATELAE	7637	LQFYEFPYT	6796
	KNLN
87	QATQDIV-	7223	SFLIYYATELAE	7638	LQFYEFPYT	6797
	KNLN
32	SASSSVSY	5778	RLLIYDTSNLAS	7639	QQWSSYPLT	6798
	MY
166	KASQSVD	5779	KLLIYAASNLES	7640	QQSNEDPWT	6799
	YD-
	GDSYMN
88	KASQSVD	7224	KLLIYAASNLES	7641	QQSNEDPWT	6800
	YD-
	GDSYMN
167	RSST-	5781	TGLIGGTNNRAP	7642	ALWYSNHWV	6801
	GAVTTSN
	YAN
168	QATQDIV-	5782	SFLIYYATELAE	7643	LQFYEFPLT	6802
	KNLN
89	QATQDIV-	7225	SFLIYYATELAE	7644	LQFYEFPLT	6803
	KNLN
169	TLSSQHST	7226	KYVMELKKDGSH	7645	GVGDTIKEQFVFV	7774
	YTIE		STGD
170	KASQSVD	5785	KLLIYAASNLES	7646	QQSNEDPPT	6805
	YD-
	GDSYMN
171	RASQDIGI	5786	KRLIYATSSLDS	7647	LQYASSPYT	6806
	SLN
172	RASENIYS	7227	QLLVYNAKNLAD	7648	QHFWGTPYT	6807
	YLA
19	SASSSVSY	5788	KLWIYSTSNLAS	7649	QQRSSFPYT	6808
	MH
90	SASSSVSY	7228	KLWIYSTSNLAS	7650	QQRSSFPYT	6809
	MH
173	KASQDIN-	5790	KTLIYRANRLVD	7651	LQYDEFPLT	6810
	SYLS
91	KASQDIN-	7229	KTLIYRANRLVD	7652	LQYDEFPLT	6811
	SYLS
174	RASQDIH	5792	KHLIYETSNLDS	7653	LQYASSPLT	6812
	GYLN
92	RASQDIH	7230	KHLIYETSNLDS	7654	LQYASSPLT	6813
	GYLN
175	KASQDVG	5794	KLLIYWASTRHT	7655	QQYSSYPFT	6814
	TAVA
93	KASQDVG	7231	KLLIYWASTRHT	7656	QQYSSYPFT	6815
	TAVA
20	KASQSVS	5796	KLLIYYASNRYT	7657	QQDYTSLPT	6816
	NDVA
94	KASQSVS	7232	KLLIYYASNRYT	7658	QQDYTSLPT	6817
	NDVA
176	RSST-	5798	TGLIGGTNNRAP	7659	ALWYSNHLV	6818
	GAVTTSN
	YAN
177	KASQSVD	5799	KLLIYVASNLES	7660	QQSHEDPRT	6819
	YD-
	GDSYMN
178	SASSSVSY	5800	KLWIYDTSKLAS	7661	FQGSGYPLT	6820
	MH
33	IT-	5801	KLLISEGNTLRP	7662	LQSDNMPLM	6821
	STDIDDD
	MN
179	RASENIYS	5802	QLLVYAATNLAD	7663	QHFWGTPYT	6822
	NLA
34	SASSSVSY	5803	KLWIYSTSNLAS	7664	QQRSTYPT	7775
	MH
180	IT-	5804	KLLISEGNTLRP	7665	LQSDNMPLT	6824
	STDIDDD
	MN
95	IT-	7233	KLLISEGNTLRP	7666	LQSDNMPLT	6825
	STDIDDD
	MN
181	RASQDISN	5806	KLLIYYTSRLHS	7667	QQGNTLPFT	6826
	YLN
96	RASQDISN	7234	KLLIYYTSRLHS	7668	QQGNTLPFT	6827
	YLN
182	SAS-	5808	KLLIYYTSSLHS	7669	QQYSKLPYT	6828
	QGISNYLN
97	SAS-	7235	KLLIYYTSSLHS	7670	QQYSKLPYT	6829
	QGISNYLN
183	RASQSISD	5810	RLLIKYASQSIS	7671	QNGHSFPWT	6830
	YLH
98	RASQSISD	7236	RLLIKYASQSIS	7672	QNGHSFPWT	6831
	YLH
35	QATQDIV-	5812	SFLIYYATELAE	7673	LQFYEFPYT	6832
	KNLN
99	QATQDIV-	7237	SFLIYYATELAE	7674	LQFYEFPYT	6833
	KNLN
100	QATQDIV-	7238	SFLIYYATELAE	7675	LQFYEFPYT	6834
	KNLN
36	RASGNIH	5815	QLLVYNAKTLAD	7676	QHFWSTPWT	6835
	NYLA
101	RASGNIH	7239	QLLVYNAKTLAD	7677	QHFWSTPWT	6836
	NYLA
184	RSST-	5817	TGLIGGTSYRAP	7678	ALWYSTHYV	6837
	GAVTTSN
	YAN
102	RSST-	7240	TGLIGGTSYRAP	7679	ALWYSTHYV	6838
	GAVTTSN
	YAN
185	RASQEIS-	5819	KRLIYAASTLDS	7680	LQYASYPWT	6839
	GYLS
103	RASQEIS-	7241	KRLIYAASTLDS	7681	LQYASYPWT	6840
	GYLS
186	KASQSVD	5821	KLLIYAASNLES	7682	QQSNEDPLPT	7776
	YD-
	GDSYMN
21	HASQNIN	5822	KLLIYKASNLHT	7683	QQGQSYPLT	6842
	VWLS
187	SASSSVSY	5823	KRWIYDTSKLAS	7684	QQWSSNPLT	6843
	MH
188	RASGNIH	5824	QLLVYNAKTLAD	7685	QHFWSTPWT	6844
	NYLA
189	RASENIYS	5825	QLLVYNAKTLAE	7686	QHHYGTPFT	6845
	YLA
190	RAS-	5826	KLWIYYTSNLAP	7687	QQFTSSLT	7777
	SSVNYMY
191	RSST-	5827	TGLIGSTNNRAP	7688	TLWYSNHWV	6847
	GAVTTSN
	YAN
192	KASQDVG	5828	KLLIYWASTRHT	7689	QQYSSYPFT	6848
	TAVA
193	KASQDIN-	5829	KTLIYRANRLVD	7690	LQYDEFPPT	6849
	SYLS
194	RASENIYS	5830	QLLVYAATNLAD	7691	QHFWGTPFT	6850
	NLA
195	RASQSISD	5831	RLLIKYASQSIS	7692	QNGHSFPYT	6851
	YLH
104	RASQSISD	7242	RLLIKYASQSIS	7693	QNGHSFPYT	6852
	YLH
37	RASENIYS	5833	QLLVYAATNLAD	7694	QHFWGTPYT	6853
	NLA
196	RSST-	5834	TGLIGGTNNRAP	7695	ALWYSNHWV	6854
	GAVTTSN
	YAN
197	IT-	5835	KLLISEGNTLRP	7696	LQSDNLPLT	6855
	STDIDDD
	MN
198	SASSSVSY	5836	KLWIYSTSNLAS	7697	QQRSSYPPT	6856
	MH
199	SASSSVSY	5837	KRWIYDTSKLAS	7698	QQWSSNPLT	6857
	MH
22	IT-	5838	KLLISEGNSLRP	7699	LQSDNLPLT	6858
	STDIDDD
	MN
200	SASSSVSS	5839	KLWIYSTSNLAS	7700	HQWSSYPPT	6859
	SYLY
201	TLSSQHST	7243	KYVMELKKDGSH	7701	GVGDTIKEQFVYV	7778
	YTIE		STGD
202	RSSQSIVH	5841	KLLIYKVSNRFS	7702	FQGSHVPWT	6861
	SNGNTYLE
203	KASQDIN-	5842	KTLIYRANRLVD	7703	LQYDEFPPT	6862
	SYLS
204	KSS-	5843	KRLIYLVSKLDS	7704	WQGTHFPWT	6863
	QSLLDSDG
	KTYLN
205	SASSSVSS	5844	KLWIYSTSNLAS	7705	HQWSSYPPT	6864
	SYLY
206	RSSQSIVY	5845	KLLIYKVSNRFS	7706	FQGSHVPPT	6865
	SNGNTYLE
207	RASENI-	5846	QLLVYAATNLAD	7707	QHFWGTPWT	6866
	YNNLA
208	SASSSVSS	5847	KLWIYSTSNLAS	7708	HQWSSYPPT	6867
	SYLY
209	SASSSVSY	5848	RLLIYDTSNLAS	7709	QQWSTYPPIT	7779
	MY
210	SASSSVSY	5849	RLLIYDTSNLAS	7710	QQWSSYPFT	6869
	MY
211	RAS-	5850	KPWIYATSNLAS	7711	QQWSSNPYT	6870
	SSVSYMH
212	RASENIYS	5851	QLLVYAATNLAD	7712	QHFWGTPWT	6871
	NLA
213	KASQDVS	5852	KLLIYWASTRHT	7713	QQHYSTPWT	6872
	TAVA
214	KSS-	5853	KRLIYLVSKLDS	7714	WQGTHFPWT	6873
	QSLLDSDG
	KTYLN
215	RSSQSIVH	5854	KFLIYKVSNRFS	7715	FQGSHVPPT	6874
	SNGNTYLE
216	IT-	5855	KLLISEGNTLRP	7716	LQSDNMPLT	6875
	STDIDDD
	MN
217	KASQDINK	5856	RLLIHYTSTLQP	7717	LQYDNLYMYT	7780
	YIA
218	HASQNIN	5857	KLLIYKASNLHT	7718	QQGQSYPYT	6877
	VWLS
219	SASSSVSY	5858	KPWIYLTSNLAS	7719	QQWSSNPPT	6878
	MY
220	KSS-	5859	KRLIYLVSKLDS	7720	WQGTHFPWT	6879
	QSLLDSDG
	KTYLN
221	SASLSVSD	5860	RLLIYDTSNLAS	7721	QQWSSYPFT	6880
	MY
222	SASSSVSS	5861	KLWIYSTSNLAS	7722	HQWSSYPPT	6881
	SYLY
223	RAS-	5862	KLWIYYTSNLAP	7723	QQFTSSPST	6882
	SSVNYMY
105	RAS-	7244	KLWIYYTSNLAP	7724	QQFTSSPST	6883
	SSVNYMY
224	IT-	5864	KLLISEGNTLRP	7725	LQSDNLPLT	6884
	NTDIDDD
	MN
106	IT-	7245	KLLISEGNTLRP	7726	LQSDNLPLT	6885
	NTDIDDD
	MN
225	KASQSVD	5866	KLLIYAASNLES	7727	QQSNEDPWT	6886
	YD-
	GDSYMN
226	RASQSISN	5867	RLLIKYASQSIS	7728	QQSNSWPFT	6887
	NLH
227	SASSSVSS	5868	KLWIYSTSNLAS	7729	HQWSSYPPT	6888
	SYLY
228	IT-	5869	KLLISEGNTLRP	7730	LQSDNMPLT	6889
	STDIDDD
	MN
229	KSS-	5870	KRLIYLVSKLDS	7731	WQGTHFPWT	6890
	QSLLDSDG
	KTYLH
230	KASQDINK	5871	RLLIHYTSTLQP	7732	LQYDNLRT	7781
	YIA
231	RSST-	5872	TGLIVGTNNRAP	7733	VLWYSNHLV	6892
	GAVTTSN
	YAN
232	KASEN-	5873	KLLIYGASNRYT	7734	GQSYSYPPT	6893
	VGTYVS
233	RASET-	5874	KLLIYRASNLES	7735	QQSNEDPRT	6894
	VDSYGYSF
	MH
234	KSS-	5875	KLLLYWASTRES	7736	QQYYSYRT	7782
	QSLLYSTN
	QKNYLA
235	KSS-	5876	KRLIYLVSKLDS	7737	WQGTHFPFT	6896
	QSLLDSDG
	KTYLN
236	KASQSVD	5877	KLLIYAASNLES	7738	QQSNEDPFT	6897
	YD-
	GDSYMN
237	TLSSQHST	7246	KYVMELKKDGSH	7739	GVGDTIKEQFVYV	7783
	YTIE		STGD
107	TLSSQHST	7247	KYVMELKKDGSH	7740	GVGDTIKEQFVYV	6899
	YTIE		STGD
238	SASSSVSY	5880	KRWIYDTSKLAS	7741	QQWSSNPLT	6900
	MH
108	SASSSVSY	7248	KRWIYDTSKLAS	7742	QQWSSNPLT	6901
	MH
239	QATQDIV-	5882	SFLIYYATELAE	7743	LQFYEFPLT	6902
	KNLN
240	RAS-	5883	KLLIYAASNQGS	7744	QQSKEVPPT	6903
	ESVDNY-
	GISFMN
241	RASQSISD	5884	RLLIKYASQSIS	7745	QNGHSFPLT	6904
	YLH
242	RSSQSIVH	5885	KLLIYKVSNRFS	7746	FQGSHVPLT	6905
	SNGDTYLE
243	SASSSVSY	5886	KRWIYDTSKLAS	7747	QQWSSNPLT	6906
	MH
244	TASESLYS-	5887	KLLIYGASNRYI	7748	AQFYSYPYT	6907
	SKHKVHYL
	A
245	TLSSQHST	7249	KYVMELKKDGSH	7749	GVGDTIKEQFVYV	7784
	YTIE		STGD
246	RASQSVST	5889	KLLIKYASNLES	7750	QHSWEIPLT	6909
	SSYSYMH
247	SASSSVSY	5890	KRWIYDTSKLAS	7751	QQWSSNPLT	6910
	MH
248	KASDHIN	5891	RLLISGATSLET	7752	QQYWSTPLT	6911
	NWLA
249	RASENIYS	5892	QLLVYNAKTLAE	7753	QHHYGTPYT	6912
	YLA
250	RASENIYS	5893	QLLVYNAKTLAE	7754	QHHYGTPPT	6913
	YLA
251	SASSSVSY	5894	KRWIYDTSKLAS	7755	QQWSSNPPT	6914
	MH
252	RAS-	5895	KLLIYAASNQGS	7756	QQSKEVPPT	6915
	ESVDNY-
	GISFMN
253	TASESLYS-	5896	KLLIYGASNRYI	7757	AQFYSYPYT	6916
	SKHKVHYL
	A
254	RSST-	5897	TGLIGGTSNRAP	7758	ALWYSTHYV	6917
	GAVTTSN
	YAN
255	SASSSI-	5898	KRWIYDTSKLAS	7759	HQRSSYPT	7785
	SYMH

HCDR1

HCDR2

HCDR3

		SEQ ID		SEQ ID		SEQ ID
	Sequence	NO:	Sequence	NO:	Sequence	NO:
265	GGTFSSY	10885	NPSGG	11147	ARDLGDPGMDV	11409
266	GGTFSNY	10886	DPSGGS	11148	ARDLGDMGMDV	11410
267	GGTFSNY	10887	NPSGGS	11149	ARDVGDRGMDV	11411
263	GGTFSSY	10888	NPSGG	11150	ARDLGDPGMDV	11412
268	GSTFSGY	10889	DPNGGG	11151	AKDIVHDGTEYFQH	11413
269	GYTFTSY	10890	NPSGGS	11152	AKDIVHDGTEYFQH	11414
270	GGTFSSY	10891	NPSGGS	11153	AREGRDHDAFDI	11415
271	GFTFTDY	10892	NPSGGS	11154	AREGRSHDAFDI	11416
272	GYTFTGY	10893	NPHSGD	11155	ARWVGTTEYYYYYYMDV	11417
273	GYTFTDY	10894	DPSGGS	11156	ATTAYYDFWSGYSMDV	11418
274	GYTFTSH	10895	DPSGGS	11157	ARDMDNWNTGYYYYMDV	11419
275	GGTFSSY	10896	NPNSGD	11158	ARDQRGGDAWDV	11420
276	GGTFSNY	10897	TPSGGS	11159	ARDTAGHFDI	11421
277	GGTFRND	10898	NPNSGN	11160	ARDNPDLDGMDV	11422
278	GGTFSSY	10899	SAYNGN	11161	ARDLVGHFDY	11423
279	GGTFSSY	10900	NPNSGG	11162	ARDGYSGSYSD	11424
264	GGTFSSY	10901	NPNSGG	11163	ARDGYSGSYSD	11425
257	GGTFSSY	10902	NPNSGG	11164	ARDGYSGSYSD	11426
280	GNTLSSH	10903	NPSGGS	11165	ARDQGSSGTFDY	11427
281	GGTLSSY	10904	NPNSGG	11166	ARDSTDVIDY	11428
282	GYIFTSY	10905	NPNSGD	11167	ARDGGTVTPTEEYYYYG-	11429
					MDV
283	GGTFSSY	10906	SVYNGN	11168	ASLDDLDY	11430
284	GHTFTSY	10907	NPNNGG	11169	ARDMVRDSAEYFQH	11431
285	GYTFITS	10908	NPSGGT	11170	ARDSSGYPIDY	11432
286	GYTFTSY	10909	IPLSGA	11171	ARGALYNWNDGWFDP	11433
258	GYTFTSY	10910	IPLSGA	11172	ARGALYNWNDGWFDP	11434
287	GFTVGSW	10911	WYEGSN	11173	ARLGTASLPYFDY	11435
288	GYTFTGY	10912	NPNRGD	11174	ARESGDGFDP	11436
289	GYTFTNY	10913	NPNSGN	11175	ARDWPNWFDP	11437
290	GYSFTDN	10914	RSDNGE	11176	AREVQLVGFDY	11438
291	GYTFSDH	10915	IPIFGT	11177	ARGSSWYLHFQH	11439
260	GYTFSDH	10916	IPIFGT	11178	ARGSSWYLHFQH	11440
292	GGTFSSY	10917	IPIFGT	11179	AKGVDRYNWNDAFDY	11441
293	GYTFTDY	10918	HSNSGG	11180	ARESSGYDSSLDY	11442
294	GGTFSSY	10919	NPNSGD	11181	TTDPRLDSSDPGY	11443
295	GGTFGNY	10920	SAYNGN	11182	ARGGMDV	11444
296	GGTFSRY	10921	YPSDGS	11183	ARDRLGDLDY	11445
261	GGTFSRY	10922	YPSDGS	11184	ARDRLGDLDY	11446
297	GGTFSSY	10923	NPNSGN	11185	ARDSIVGGYPFDY	11447
298	GYTFTSY	10924	TPIFGT	11186	AREGYSSSWHDDAFDI	11448
299	GGTFSNY	10925	DPSGGS	11187	ARDLGDYGLDS	11449
300	GYTFTGY	10926	NPNSGD	11188	ATGGSDSSGYYYEGYFQH	11450
301	GGTFSSY	10927	SPNSGN	11189	ARDKGGYYDSSGYYWY	11451
302	GFSLSSY	10928	SSNGGS	11190	ARVGDGDGYNPDFDY	11452
303	GYTFTSY	10929	DPTSGA	11191	AKDPIVATEVDY	11453
304	GGTFSSY	10930	SPNSGN	11192	ARDSGAFDI	11454
305	GVTISNY	10931	NPNSGN	11193	AREGLLDAFDI	11455
306	GGTFSRY	10932	NPYDGN	11194	ARGGRHHDAFDI	11456
307	GGTFSSY	10933	NPSGDG	11195	ARDISNDAFDI	11457
308	GYILTGH	10934	SAYNGD	11196	ARGSSWDDAFDI	11458
309	GFTFSNH	10935	GAGGG	11197	AREGWNDDVFDI	11459
310	GGTFSSY	10936	NPSAGT	11198	ARDGNFGAFDI	11460
311	GYSFTTY	10937	IPIFGT	11199	ARDKSGWNYGSGSYN-	11461
					DAFDI
312	GYAFTGY	10938	NPNSGK	11200	ARDGGLDFDY	11462
313	GYTFTTY	10939	NPNTGD	11201	AKDPAVTPDAFDI	11463
314	GGTLSSY	10940	DPSGGG	11202	AGSLYYYGMDV	11464
315	GGTFGSS	10941	IPIFGT	11203	AKEDDILPPRAFDI	11465
316	GFTFDDY	10942	SGGGGV	11204	ARVYSSGWLDAFDI	11466
317	GGTFSSY	10943	SGYNGN	11205	ASSDVSPDAFDI	11467
318	GGTQNIY	10944	NPNSGN	11206	ATPTSSSDDAFDI	11468
319	GGTFSSY	10945	NPNSGG	11207	ARASRGDDAFDI	11469
320	GIPFTSD	10946	NPSGGS	11208	ARERYEGGY-	11470
					SSGPGNYYYGMDV
321	GGTFSNY	10947	NPNSGN	11209	ARDDDYGDYPV	11471
322	GDTFSDH	10948	NPKIGN	11210	VYDSSGYDAFDI	11472
323	GYTFTSY	10949	NPGTGG	11211	ARETPSDYYDSSGYYYN-	11473
					DAFDI
324	GGTFSSY	10950	IPSGG	11212	ARDLGTTFDI	11474
325	GYTFTAY	10951	NPDNDN	11213	AKDIAVAALAYGMDV	11475
326	GFTFSSY	10952	SYDGSD	11214	ARQSLYYYYGMDV	11476
327	GYTFTDY	10953	STFTGN	11215	ARDAPLAAAGTDYYYG-	11477
					MDV
262	GYTFTDY	10954	STFTGN	11216	ARDAPLAAAGTDYYYG-	11478
					MDV
328	GFTFSSY	10955	SDDGIT	11217	ARDDSSGYGGMDV	11479
329	GFTFSSY	10956	SYDGGD	11218	ASGSLVLGYYYMDV	11480
330	GYTFTNY	10957	NPNTGG	11219	ATGGGGSYYDAFDV	11481
331	GGTFSSY	10958	NPNSGN	11220	ARDIGEGYSMDV	11482
332	GFTFSNH	10959	SYDGSN	11221	AREEKYSSSWY-	11483
					VGVDAFDI
333	GFTFSSS	10960	SGSGDN	11222	ARDQEDYYYDSSGYG-	11484
					MDV
334	GGTFSSH	10961	IPIFGT	11223	AKGDW-	11485
					GIVVVPAAIGAFDI
335	GYTFTAY	10962	SPVFGS	11224	ARDLGYYDSSGYRYDAF	11486
					DI
336	GYTFTSY	10963	SPMFGT	11225	AKDGWYYGMDV	11487
337	GGTFSSY	10964	NPNSGG	11226	ARGEAGNLDWYFDL	11488
338	GGTFSNY	10965	NPNNGD	11227	AREDVWYFDL	11489
339	GYTFTTY	10966	STYDGK	11228	ALHLGGDWYFDL	11490
340	GYTFTGY	10967	NPNTGA	11229	ARQHGDYDWYFDL	11491
341	GDTFTTY	10968	NPNSGN	11230	ARDSGRH	11492
342	GGTFSSY	10969	IPMLGI	11231	VREEVAGANWFDP	11493
343	GYTFTSY	10970	NPSGGS	11232	AREGDYGSGEFDY	11494
344	GYTFTSS	10971	NPRSGN	11233	ARERDDYGDYGWLDY	11495
345	GYTFTGY	10972	NPSGGS	11234	ARDLYDSSGY-	11496
					WHYYYYMDV
346	GGTFSSY	10973	NPNSGG	11235	ARFSGYDYVDY	11497
347	GGTFSSY	10974	NPNGGN	11236	ARDVGEDFDL	11498
348	GYTFTSY	10975	NPADGD	11237	ARDFDWLFAMDV	11499
349	GGTFSNY	10976	NPNGGT	11238	AKHGDHGFYV	11500
350	GGTFSSY	10977	NPNVGS	11239	AREDSGTSWFDP	11501
351	GYTFTSY	10978	NPSDGS	11240	ARDDRGSNYYYGMDV	11502
352	GYTFTAY	10979	NPNSGT	11241	ARDSSDYYGDYRADAFDI	11503
353	GYTFTSY	10980	SPSGDA	11242	VKGLDH	11504
354	GFSFSDY	10981	GGIGDS	11243	ARMNYGDSNYYYYYG-	11505
					MDV
355	GYTFTSY	10982	SPSDGS	11244	ARGAVGFDY	11506
356	GYTFTSY	10983	NTYSGY	11245	TTDDFLSFGY	11507
357	GYMFTDY	10984	IPYFGT	11246	ARSISGSYVLDAFDI	11508
358	GYTFNSY	10985	IPIFGT	11247	ARDWGYGDYADDAFDI	11509
359	GGTFSNN	10986	NPIYGS	11248	AADWRGFDY	11510
360	GYTFTEY	10987	NPHNGD	11249	AREGDYLGYPIDC	11511
361	GFTFSDY	10988	WQDGNV	11250	ARDGNSGYVF	11512
362	GYTFTTY	10989	NPNTGD	11251	ARTAEAVAGLPAFDY	11513
363	GGTSNNY	10990	IPLFGT	11252	ARVTLYGDYDY	11514
364	GYSLITH	10991	NPSDGV	11253	AREYYGEGFDY	11515
259	GYSLITH	10992	NPSDGV	11254	AREYYGEGFDY	11516
365	GGTFSSY	10993	NPSGGS	11255	ARDLGDTAMDG	11517
366	GYTFTSY	10994	TPSGGS	11256	ARDGGLASFDY	11518
367	GGTFSSY	10995	NPNSGN	11257	ARGGGWAMTDAFDI	11519
368	GFTFDDY	10996	YSGGD	11258	TRKEYYYDSSGYLRLFDY	11520
369	GYTFTDY	10997	NPIFGT	11259	ARDISGYDYYYYGMDV	11521
370	GGTLNNY	10998	DPSDGT	11260	ARSDYDFWSGLGGYFDY	11522
371	GGTFSSY	10999	DPNSGG	11261	ARDSAEWELGGSFDY	11523
372	GFTFSNH	11000	GVNGD	11262	AREGLVFSGRGHWYFDL	11524
373	GGTFSNY	11001	NPNGGN	11263	ARDYEDADFDG	11525
374	GYTFSDH	11002	NPDSGN	11264	ARDSTSGVDY	11526
375	GFTFSSY	11003	SYDGHD	11265	ARGEQQLEGFYYYYG-	11527
					MDV
376	GFTFSSY	11004	SYDGSK	11266	ASDYGDYGTYDY	11528
377	GFTFSSY	11005	SGGGDD	11267	AREPLAYCGG-	11529
					DCPGGFDY
378	GFTFSDH	11006	GTGGD	11268	ARHEDTAIFLDY	11530
379	GYTFTSY	11007	SPSDGS	11269	ARDGYDAWSYGMDV	11531
380	GYTFTGY	11008	NPNSGN	11270	ARDGVTGTDY	11532
381	GFAFSSY	11009	SGAGDS	11271	AREPTTVTDDWYFDL	11533
382	GFAFSSH	11010	SGNGDN	11272	ARDRAPEYFDL	11534
383	GGTFSSY	11011	NPNSGG	11273	ARDDYGDYGGGMDV	11535
384	GYTFTDY	11012	NPNSGH	11274	AKDTSPRYGDGFFDY	11536
385	GFTFSSY	11013	SYDGSN	11275	ARESGFSAEYFQH	11537
386	GGTFSSY	11014	NPSGGS	11276	ARATGLYCSGSCFDY	11538
388	RSILDFN	14119	ARAGA	14120	RVFDLPNDY	14121

LCDR1

LCDR2

LCDR3

		SEQ ID		SEQ ID		SEQ ID
	Sequence	NO:	Sequence	NO:	Sequence	NO:
265	RASQDISN	12194	KLLIYDASNLET	13104	QQSYSTPLT	12714
	YLN
266	RASQSIS-	12195	KLLIYAASSLQS	13105	QQSYSTPLT	12715
	SYLN
267	QASQDIS	12196	KLLIYKASSLET	13106	QQSFSSPLT	12716
	NYLN
263	RASQDISN	12197	KLLIYDASNLET	13107	QQSYSTPLT	12717
	YLN
268	RASQNVN	12198	KLLIYEASSLQS	13108	QQANSFPFT	12718
	TWLA
269	RASQSISD	12199	KLLIYAASSLQS	13109	AQHNHYPYT	12719
	WLA
270	KSS-	12200	KLLIYWASTRES	13110	QQYYTTPFT	12720
	QSVLSSSY
	NKNYLA
271	KSS-	12201	KLLIYWASTRAS	13111	QQYYSTPFT	12721
	QSVLSSSY
	NKNYLA
272	RAS-	12202	KLLIYDASHLEA	13112	QQANSFPIT	12722
	QAIRDDLG
273	RASQGVG	12203	KLLIYAASTLQT	13113	QQASSFPLT	12723
	NDLA
274	RASQI-	12204	KLLIYAASSLQS	13114	QQSYTFPVT	12724
	IGTNLA
275	RASQSIST-	12205	KLLIYDASSLES	13115	QQSYSTPFT	12725
	WLA
276	KSS-	12206	KLLIYWASTRES	13116	QQYYGSPLT	12726
	QSVLSSS-
	NNKNYLA
277	KSS-	12207	KLLIYWASTRES	13117	QQYYSSPPT	12727
	QSVLSSSY
	NKNYLA
278	KSS-	12208	KLLIYWASTRES	13118	QQYYSSPPT	12728
	QSVLSSSY
	NKNYLA
279	KSS-	12209	KLLIYWASTRES	13119	QQYYSTPWT	12729
	QSVLSSSY
	NKNYLA
264	KSS-	12210	KLLIYWASTRES	13120	QQYYSTPWT	12730
	QSVLSSSY
	NKNYLA
257	KSS-	12211	KLLIYWASTRES	13121	QQYYSTPWT	12731
	QSVLSSSY
	NKNYLA
280	KSS-	12212	KLLIYWASTRAS	13122	QQYYGSPPT	12732
	QSVLSSSY
	NKNYLA
281	QASQDIR	12213	KLLIYDASTLQS	13123	QQAYSFPWT	12733
	NYLN
282	QASQDIS	12214	KLLIYNASNLET	13124	QQLNSYPFT	12734
	NYLN
283	QASQSIST	12215	KLLIYAASTLRS	13125	LQHYTYPLT	12735
	WLA
284	RASEDI-	12216	KLLIYAASTLQS	13126	QQSHTIPWT	12736
	STYLA
285	RASH-	12217	KLLIYAASTLQS	13127	QQSYSSPYT	12737
	HISDFLN
286	RASQDIG	12218	KLLIYDASSLQS	13128	QQANSFPLT	12738
	DYLA
258	RASQDIG	12219	KLLIYDASSLQS	13129	QQANSFPLT	12739
	DYLA
287	RASQDIRS	12220	KLLIYAASSLQS	13130	QQSYTAPPT	12740
	YLA
288	RASQDIS-	12221	KLLIYAASTLQS	13131	LQHNTYPLT	12741
	NNLN
289	RASQDIS-	12222	KLLIYDASSLQS	13132	QQAISFPLT	12742
	NWLA
290	RASQGIA	12223	KLLIYAASSLQS	13133	QQADSFPLT	12743
	NYLA
291	RASQGIAS	12224	KLLIYAASTLQP	13134	QQFDSYPIT	12744
	YLA
260	RASQGIAS	12225	KLLIYAASTLQP	13135	QQFDSYPIT	12745
	YLA
292	RASQGISN	12226	KLLIYAASRLQS	13136	QQSSIIPFT	12746
	YLA
293	RASQGISN	12227	KLLIYAASTLQS	13137	QQAYSFPYT	12747
	YLA
294	RASQSIGR	12228	KLLIYDASNLET	13138	QQSYSTPRT	12748
	WLA
295	RASQSINS	12229	KLLIYDTSSLQS	13139	QQTYSTPYT	12749
	WLA
296	RASQSISS	12230	KLLIYAASTLQS	13140	QQGYSTPYI	12750
	WLA
261	RASQSISS	12231	KLLIYAASTLQS	13141	QQGYSTPYI	12751
	WLA
297	RASQSIS-	12232	KLLIYAASSLQS	13142	QQTDSIPIT	12752
	SYLN
298	RASQSIS-	12233	KLLIYAASTLQS	13143	QQSYSIPYT	12753
	SYLN
299	RASQTIRS	12234	KLLIYKASSLES	13144	QQTYTIPIT	12754
	YLN
300	RASQTISN	12235	KLLIYAASTLQS	13145	QQANSFPPT	12755
	WLA
301	RASQYIGS	12236	KLLIYDASNLET	13146	QQVDSYPLT	12756
	YLN
302	RSSQSLLH	12237	QLLIYLGSNRAS	13147	MQGTHWPPT	12757
	SNGYNYL
	D
303	RSSQSLLH	12238	QLLIYFGSNRAS	13148	MQALQAPVS	12758
	SNGYNYL
	D
304	KSS-	12239	KLLIYWASSRQS	13149	QQYYSTPLT	12759
	QSVLSSSY
	NKNYLA
305	KSS-	12240	KLLIYWASVRES	13150	QQYYSTPIT	12760
	QSVSSSSY
	NKNYLA
306	KSTQNVLS	12241	KLLIYWASTRES	13151	QQYYSTPFT	12761
	SSNNN-
	SYLA
307	QASQDIG	12242	KLLIYAASSLQS	13152	QQTYNTPLT	12762
	NYLN
308	QASQDIS	12243	KLLIYEASTLQS	13153	QQSYSTPFT	12763
	NYLN
309	QASQDIST	12244	KLLIYRASTLES	13154	QQSYSIPLT	12764
	WLA
310	RASQNIN-	12245	KLLIYAASRLQS	13155	QQSYSAPVT	12765
	NYLN
311	RASQNINT	12246	KLLIYAASSLQS	13156	QQAYSFPFT	12766
	WLA
312	RASQRIGN	12247	KLLIYAASSLQS	13157	QQSYSTPLT	12767
	YLN
313	RASQSIST	12248	KLLIYAASTLQS	13158	QQSYRTVT	12768
	YLN
314	RASQSVG	12249	RLLIYGASTRAT	13159	QQYDSSSQT	12769
	SYLA
315	RASRSVST	12250	RLLIYGASTRAT	13160	QQYDGSPYT	12770
	YLA
316	RSSQSLLH	12251	QLLIYDASNLET	13161	MQALQTPPA	12771
	SNGYNYL
	D
317	KSS-	12252	KLLIYWASTRES	13162	QQYYSAPPT	12772
	QSVLSSSY
	NKNFLA
318	KSS-	12253	KLLIYWASTRES	13163	QQYYSDPIT	12773
	QSVLSSSY
	NKNFLA
319	KSS-	12254	KLLIYWASARES	13164	QQYYSIPIA	12774
	QSVLSSSY
	NKNYLA
320	KSS-	12255	KLLIYWASTRDS	13165	QQYYSIPYT	12775
	QSVLSSSY
	NKNYLA
321	KSS-	12256	KLLIYWASTRAS	13166	QQYYTTPPT	12776
	QSVLSTSY
	NKNYLA
322	KSS-	12257	KLLIYWASTRQS	13167	QQYYSTPYT	12777
	QSVLSTSY
	NRNFLA
323	KSS-	12258	KLLIYWASTRES	13168	QQYYSTPLT	12778
	QSVLYSSN
	NKNYLA
324	QASQDIS	12259	KLLIYAASSLQS	13169	QQSYSTPT	12779
	NYLN
325	QASQDIS	12260	KLLIYGASTLQS	13170	QEADSFPLT	12780
	NYLN
326	RASQGIRN	12261	KLLIYDASSLHS	13171	QQAYSFPWT	12781
	DLG
327	RASQGISN	12262	KLLIYKASSLES	13172	QQSYNTPFT	12782
	YLA
262	RASQGISN	12263	KLLIYKASSLES	13173	QQSYNTPFT	12783
	YLA
328	RASQSINR	12264	KLLIYSASNLQS	13174	QQSYNTPLT	12784
	WLA
329	RASQSINT	12265	KLLIYAASSLQS	13175	QQANSFPFT	12785
	WLA
330	RASQSIRT-	12266	KLLIYDASSLET	13176	QQLNSYPLT	12786
	WLA
331	RASQSIRT	12267	KLLIYAASTLQS	13177	QQSYSAPLT	12787
	YLN
332	RASQSIST	12268	KLLIYAASSLHS	13178	QQSYSTPLT	12788
	YLN
333	RASQSIT-	12269	KLLIYAASTLQS	13179	QQSYSTPLT	12789
	TYLN
334	RSSQSLLH	12270	QLLIYAASSLQS	13180	MQARQTPLT	12790
	SNGYNYL
	D
335	RSSQSLLH	12271	QLLIYGASSLQS	13181	MQTLQTPFT	12791
	SNGYNYL
	D
336	RSSQSLLH	12272	QLLIYLGSDRAS	13182	MQALQTPLT	12792
	SNGYNYL
	D
337	KSSQTVF-	12273	KLLIYWASTRES	13183	QQYYSTPLT	12793
	STSYN-
	KNYLA
338	KTSQSVF-	12274	KLLIYWASTRES	13184	QQYYSSPPT	12794
	STSYN-
	RDYLA
339	RASQSISS	12275	KLLIYDASTLQS	13185	QQSYSTPFT	12795
	WLA
340	RASQSIS-	12276	KLLIYDASNLKT	13186	QQSYSFPT	12796
	SYLN
341	RASQSVSS	12277	RLLIYDTSSRAT	13187	QQYYDTPYT	12797
	YLA
342	KSS-	12278	KLLIYLASTREP	13188	QQYYSTPPT	12798
	QSVLYSSN
	NKNYLA
343	KSS-	12279	KLLIYWASTRES	13189	QQYYSTPLT	12799
	QSVLSSSY
	NKNYVA
344	QASQDIS	12280	KLLIYAAASLQS	13190	QQTYSTPWT	12800
	NYLN
345	RASQDIN-	12281	KLLIYAASSLQS	13191	QQSSSFPLT	12801
	TYLA
346	QASQDIS	12282	KLLIYAASSLQS	13192	QQLYNFPYT	12802
	NYLN
347	RASQSISR	12283	KLLIYGASTRES	13193	QQSYNTPLT	12803
	YLA
348	RASQTLSG	12284	KLLIYGASTLQG	13194	QQYYSYPPT	12804
	WLA
349	FASQDI-	12285	KLLIYEASNLET	13195	QQSYSTPLT	12805
	INYLN
350	RASQSIS-	12286	KLLIYDVFNLGT	13196	QQSYSSPFT	12806
	SYLN
351	QASQDIS	12287	KLLIYMASNLES	13197	QQTNSFPLT	12807
	NYLN
352	RASQSIS-	12288	KLLIYDASNLET	13198	QQSYSTPLT	12808
	SYLN
353	RSSQSLLH	12289	QLLIYLGSNRAS	13199	MQALQSPWT	12809
	SNGYNYL
	D
354	KSS-	12290	KLLIYWASTRES	13200	QQYYSSPLT	12810
	QSVLYSSN
	NKNYLA
355	RSSQSLLH	12291	QLLIYLGSNRAS	13201	MQALQTPPS	12811
	SNGYNYL
	D
356	RAS-	12292	KLLIYKASRLES	13202	QQSYKTPYT	12812
	ESVST-
	WLA
357	KSS-	12293	KLLIYWASTRES	13203	QQYFTTPLT	12813
	QSVLYSSN
	NKNYLA
358	RASQSIS-	12294	KLLIYAASSLQS	13204	QQSYSTPYT	12814
	SYLN
359	KSS-	12295	KLLIYWASTRAS	13205	QQYYDTPLT	12815
	QSVLSSSY
	NKNYLA
360	RASQSIS-	12296	KLLIYKASTLES	13206	QQNDSIPIT	12816
	SYLN
361	RASQSISR	12297	KLLIYDASNLET	13207	LQDYSYPLT	12817
	WLA
362	KTSQSVF-	12298	KLLIYWASTRAA	13208	QQYYYTST	12818
	STSYN-
	RDYLA
363	RASQSIN-	12299	KLLIYAASSLQS	13209	QQANSFPPT	12819
	RYLN
364	RASQGISN	12300	KLLIYSASNLQS	13210	QQSYSTPLT	12820
	YLA
259	RASQGISN	12301	KLLIYSASNLQS	13211	QQSYSTPLT	12821
	YLA
365	RASQSIDS	12302	KLLIYKASTLES	13212	QQSYSAPLT	12822
	YLN
366	RASQDIST	12303	KLLIYDASNLET	13213	QQVNSDPYT	12823
	WLA
367	QASQDIS	12304	KLLIYAASTLES	13214	QQGDSLPLT	12824
	NYLN
368	RASQGISN	12305	KLLIYAASSLQS	13215	QQSDSFPYT	12825
	YLA
369	RASQSVST	12306	RLLIYGASTRAT	13216	QQHDSYPLT	12826
	YLA
370	RASQGIRN	12307	KLLIYAASSLQS	13217	QQANSFPPT	12827
	DLG
371	RAS-	12308	KLLIYKASNLES	13218	QQTDSTFIT	12828
	ESISTYLN
372	RASRNIHD	12309	KLLIYAASTLQT	13219	QQTYSTPPT	12829
	YLN
373	RASQSND	12310	KLLIYKASTLES	13220	QQSYSSPLT	12830
	SYLN
374	RASQSISD	12311	KLLIYAASTLQS	13221	QQSYSSPYT	12831
	FLN
375	QASQDIS	12312	KLLIYAASSLQS	13222	QQANRFPLT	12832
	NYLN
376	QASQDIS	12313	KLLIYKASNLQS	13223	QQSYNFPAT	12833
	NYLN
377	RSSQSLLH	12314	QLLIYLGSNRAS	13224	MQGTHWPET	12834
	SNGYNYL
	D
378	RASQSIS-	12315	KLLIYDASNLET	13225	QQSYSTPLT	12835
	SYLN
379	RASQGISD	12316	KLLIYDASNLET	13226	QQSYILPLT	12836
	YLA
380	RASQDIN	12317	KLLIYAASSLQS	13227	QQSYSAPYT	12837
	DFLA
381	RASQSISN	12318	KLLIYAASKLES	13228	QQSYSSPWT	12838
	WLA
382	RASQGIDS	12319	KLLIYAASTLES	13229	QQAYSFPLT	12839
	WLA
383	RASQNIGT	12320	KLLIYRASSLES	13230	QQAYSFPWT	12840
	WLA
384	RASQNIN	12321	KLLIYKASTLQS	13231	QQADSFPPT	12841
	NWLA
385	RASQDIS-	12322	KLLIYAASTLQS	13232	QQLNRYPIT	12842
	SYLA
386	RASQDISN	12323	KLLIYAASILHS	13233	QQYDSSFIT	12843
	YLA

TABLE 24
CDRs using the IMGT Numbering Scheme
Table 6-IMGT CDR Sequences

Binder		SEQ ID		SEQ ID		SEQ
Name	Sequence	NO:	Sequence	NO:	Sequence	ID NO:

HCDR1

HCDR2

HCDR3

109	GYTFSSYW	4361	ILPGSGST	4875	ARRAYGYDGGFDY	4105
110	GYTFSSYW	4362	ILPGSGST	4876	ARRAYGYDEGFDY	4106
111	GYTFSSYW	4363	ILPGSDST	4877	ARRAYGYDEGFDY	4107
112	AYTFSIYW	4364	ILPGSGST	4878	ARRAYGYDGGFDY	4108
1	GYTFSSYW	4365	IFPGSGHT	4879	ARRGYGYDEGFDY	4109
113	GYTFSSYW	4366	ILPGSGST	4880	ARRGYGYDEGFDY	4110
114	GYTFSSYW	4367	ILPGSGST	4881	ARRGYGYDEGFDY	4111
115	GYTFSNYW	4368	ILPGSGST	4882	ARRGYGYDEGFDY	4112
23	GYTFSSYW	4369	ILPGSGST	4883	ARRGYGYDEGFDY	4113
116	GYTFSSYW	4370	ILPGSGYT	4884	ARRGYGYDEGFDY	4114
117	GYTFSSYW	4371	ILPGSGST	4885	ARRAYGYDEGFDY	4115
2	GYTLSSYW	4372	ILPGSGST	4886	ARRGYGYDEGFDY	4116
118	GYTFSSYW	4373	VLPGSGST	4887	ARRAYGYDEGFDY	4117
119	GYTFSSYW	4374	ISPGSGST	4888	ARRGYGYDEGFDY	4118
120	GYTFGTYW	4375	ILPGSGTP	4889	ARRAYGYDAGFDY	4119
121	GYTFSSYW	4376	ILPGSGST	4890	ARRGYGYDEGFDY	4120
122	GYTFSSYW	4377	ILPGSGRT	4891	ARRGYGYDEGFDY	4121
123	GYTFSSYW	4378	ILPGSGRT	4892	ARRGYGYDEGFDY	4122
38	GYTFSSYW	4379	ILPGSGST	4893	ARRAYGYDEGFDY	4123
39	GYTFSSYW	4380	VLPGSGST	4894	ARRAYGYDEGFDY	4124
40	GYTFSSYW	4381	ILPGSGRT	4895	ARRGYGYDEGFDY	4125
41	GYTFSSYW	4382	VLPGSGST	4896	ARRAYGYDEGFDY	4126
42	GYTFSSYW	4383	ILPGSGRT	4897	ARRGYGYDEGFDY	4127
43	GYTFSSYW	4384	ILPGSGST	4898	ARRAYGYDGGFDY	4128
44	GYTFSSYW	4385	ILPGSDST	4899	ARRAYGYDEGFDY	4129
45	AYTFSIYW	4386	ILPGSGST	4900	ARRAYGYDGGFDY	4130
46	GYTFSSYW	4387	IFPGSGHT	4901	ARRGYGYDEGFDY	4131
47	GYTFSNYW	4388	ILPGSGST	4902	ARRGYGYDEGFDY	4132
47	GYTFSNYW	4388	ILPGSGST	4902	ARRGYGYDEGFDY	4132
48	GYTFSSYW	4389	ILPGSGST	4903	ARRGYGYDEGFDY	4133
48	GYTFSSYW	4389	ILPGSGST	4903	ARRGYGYDEGFDY	4133
49	GYTFSSYW	4390	ILPGSGYT	4904	ARRGYGYDEGFDY	4134
50	GYTLSSYW	4391	ILPGSGST	4905	ARRGYGYDEGFDY	4135
51	GYTFSSYW	4392	ISPGSGST	4906	ARRGYGYDEGFDY	4136
52	GYTFGTYW	4393	ILPGSGTP	4907	ARRAYGYDAGFDY	4137
53	GYTFSSYW	4394	ILPGSGST	4908	ARRGYGYDEGFDY	4138
54	GYTFSSYW	4395	ILPGSGRT	4909	ARRGYGYDEGFDY	4139
55	GYTFSNYW	4396	ILPGSGST	4910	ARRGYGYDEGFDY	4140
56	GYTFSSYW	4397	ILPGSGST	4911	ARRGYGYDEGFDY	4141
3	GYSFTGYY	4398	ISSYNGAT	4912	ARGRYGEYFDY	4142
4	GYSFTGYY	4399	ISSYNGVT	4913	ARGRYGDYFDY	4143
5	GYSFTGYY	4400	ISSYNGVT	4914	ARGRYGDYFDY	4144
6	GYSFTGYY	4401	ISSYNGVT	4915	ARGRYGDYFDY	4145
7	GYSFTGYY	4402	ISSYNGAN	4916	ARGRYGDYFDY	4146
8	GYSFTGYY	4403	ISSYNGVT	4917	ARGRYGDYFDY	4147
9	GYSFTGYY	4404	ISSYNGVT	4918	ARGRYGDYFDY	4148
10	GYSFTGYY	4405	ISSYNGVT	4919	ARGRYGDYFDY	4149
11	GYSFTGYY	4406	ISSYNGVT	4920	ARGRYGDYFDY	4150
12	GYSFTGFY	4407	ISSYNGAT	4921	ARGRYGDYFDY	4151
13	GYSFTGYY	4408	ISSYNGAT	4922	ARGRYGDYFDY	4152
57	GYSFTGYY	4409	ISSYNGVT	4923	ARGRYGDYFDY	4153
58	GYSFTGYY	4410	ISSYNGAT	4924	ARGRYGEYFDY	4154
124	GFSLSSYG	4411	IWRGGST	4925	AKNLYGHYVMDY	4155
125	GFSVTSYG	4412	IWRGGST	4926	AKNLYGHYVMDY	4156
126	GFSLTSYG	4413	IWRGGST	4927	AKNLYGHYVMDY	4157
127	GFSLTRYG	4414	IWRGGST	4928	AKNLYGHYVMDY	4158
128	GFSVTTYG	4415	IWRGGST	4929	AKNLYGHYVMDY	4159
129	GFSVTSYG	4416	IWRGGST	4930	AKNLYGHYVMDY	4160
130	GFSLTRYG	4417	IWRGGST	4931	AKNLYGHYVMDY	4161
59	GFSLSSYG	4418	IWRGGST	4932	AKNLYGHYVMDY	4162
60	GFSVTSYG	4419	IWRGGST	4933	AKNLYGHYVMDY	4163
61	GFSLTSYG	4420	IWRGGST	4934	AKNLYGHYVMDY	4164
62	GFSLTRYG	4421	IWRGGST	4935	AKNLYGHYVMDY	4165
63	GFSVTTYG	4422	IWRGGST	4936	AKNLYGHYVMDY	4166
131	GYTFTSYW	4423	IHPNSGST	4937	ARWGDGYSFAY	4167
132	GYTFTSYW	4424	IHPNSGST	4938	ARWGDGYSFAY	4168
133	GYTFTTYW	4425	IHPNSDNT	4939	ARWGDGYSFAY	4169
14	GYTFTSYW	4426	IHPNSGTT	4940	ARWGDGYSFAY	4170
134	GYTFTSYW	4427	IHPNSGNT	4941	ARWGDGYSFAY	4171
64	GYTFTSYW	4428	IHPNSGST	4942	ARWGDGYSFAY	4172
65	GYTFTSYW	4429	IHPNSGTT	4943	ARWGDGYSFAY	4173
135	GYTFTDYV	4430	IYPGSGST	4944	ARRGERGPWFAY	4174
136	GYTFTDYV	4431	IYPGSGSS	4945	ARRGERGPWFAY	4175
137	GYTFTDYV	4432	IYPGSGSS	4946	ARRGERGPWFAY	4176
138	GYTFTDYV	4433	IYPGSGSS	4947	ARRGERGPWFAY	4177
15	GYTFTDYV	4434	IYPGSGSS	4948	ARRGERGPWFAY	4178
66	GYTFTDYV	4435	IYPGSGST	4949	ARRGERGPWFAY	4179
67	GYTFTDYV	4436	IYPGSGSS	4950	ARRGERGPWFAY	4180
68	GYTFTDYV	4437	IYPGSGSS	4951	ARRGERGPWFAY	4181
69	GYTFTDYV	4438	IYPGSGSS	4952	ARRGERGPWFAY	4182
24	GYTFTNYW	4439	IDPSDSET	4953	ATYDVYYRFAY	4183
139	GYTFTNYW	4440	IDPSDSET	4954	ATYDGYYRFAY	4184
140	GYTFTNYW	4441	IDPSDSET	4955	ATYDIYYRFAY	4185
16	GYTFTSYW	4442	IHPNSGST	4956	ARPGGYGFVY	4186
141	GYTFTSYW	4443	IHPNSDST	4957	ARPGGYGFAD	4187
142	GYTFTTYW	4444	IHPNSGST	4958	ARPGGYGFTY	4188
143	GYTFTSYW	4445	IHPNSGSP	4959	ARPGGYGFAY	4189
70	GYTFTSYW	4446	IHPNSGSP	4960	ARPGGYGFAY	4190
25	GYTFTSYW	4447	IYPSDSYT	4961	TRGNYIDY	4191
144	GYTFTSYW	4448	IYPSDSYT	4962	TRGNYIDY	4192
145	GYTFTDYW	4449	IYPSDSYT	4963	TRGNYIDY	4193
146	GYTFTDYV	4450	IYPGSGSS	4964	ARPGDLGFAY	4194
147	GYTFTDYV	4451	IYPGSGSN	4965	ARPGDLGFAY	4195
148	GYTFTDYV	4452	IYPGSGSS	4966	ARPGDLGFAY	4196
71	GYTFTDYV	4453	IYPGSGSS	4967	ARPGDLGFAY	4197
72	GYTFTDYV	4454	IYPGSGSS	4968	ARPGDLGFAY	4198
73	GYTFTDYV	4455	IYPGSGSN	4969	ARPGDLGFAY	4199
74	GYTFTDYV	4456	IYPGSGSS	4970	ARPGDLGFAY	4200
74	GYTFTDYV	4456	IYPGSGSS	4970	ARPGDLGFAY	4200
75	GYTFTDYV	4457	IYPGSGSS	4971	ARPGDLGFAY	4201
75	GYTFTDYV	4457	IYPGSGSS	4971	ARPGDLGFAY	4201
76	GYTFTDYV	4458	IYPGSGSS	4972	ARPGDLGFAY	4202
149	GFSLTNYG	4459	VWAGGIT	4973	ARGDGYDDGYAMDY	4203
150	GFSLTSYG	4460	LWAGGIT	4974	ARGDGYDDGYAMDY	4204
26	GFSLTSYG	4461	IWAGGTT	4975	ARGDGYDDGYAMDY	4205
77	GFSLTNYG	4462	VWAGGIT	4976	ARGDGYDDGYAMDY	4206
78	GFSLTSYG	4463	LWAGGIT	4977	ARGDGYDDGYAMDY	4207
79	GFSLTSYG	4464	IWAGGTT	4978	ARGDGYDDGYAMDY	4208
151	GYSFTSYW	4465	IDPSDSET	4979	ARTRNY	4209
152	GYSFTSYW	4466	IDPSDSET	4980	ARTRNY	4210
153	GYSFTSYW	4467	IDPSDSET	4981	ARTRNY	4211
154	GFNIKDYY	4468	IDPENGDT	4982	NAPLLRYSSAMDY	4212
155	GFNIKDYY	4469	IDPENGDT	4983	NAPLLRYSSSMDY	4213
156	GFNIKDYY	4470	IDPENGDT	4984	NVALLRYSSAMDY	4214
80	GFNIKDYY	4471	IDPENGDT	4985	NAPLLRYSSAMDY	4215
81	GFNIKDYY	4472	IDPENGDT	4986	NAPLLRYSSSMDY	4216
82	GFNIKDYY	4473	IDPENGDT	4987	NVALLRYSSAMDY	4217
17	GFNIKDTS	4474	IDPANGNT	4988	ARGPDDGYFYYYSMDY	4218
157	GYTFSNYY	4475	INPSNGDT	4989	TSYYTHEAYYYAMDC	4219
27	GSTFTTYY	4476	INPSNGGT	4990	TSYYTHETYYYAMDY	4220
158	GFNIKDYY	4477	IDPEDGDT	4991	TPYSIYDAMDY	4221
159	GYTFTDYV	4478	IYPGSGST	4992	ARRGERGPWFAY	4222
83	GYTFTDYV	4479	IYPGSGST	4993	ARRGERGPWFAY	4223
160	GYSFTDYG	4480	ISTYYGDA	4994	ARQMDYDYTYYYAMDY	4224
28	GYTFTSYW	4481	IDPSDSYT	4995	ARAEYGYGNYPWFAY	4225
84	GYTFTSYW	4482	IDPSDSYT	4996	ARAEYGYGNYPWFAY	4226
29	GYTFTSYW	4483	IHPSDSDT	4997	AIPYYYGGWYFDV	4227
161	GYTFTDYV	4484	IYPGSGST	4998	ARMDGPWFAY	4228
30	GFTFSSYG	4485	ISSGGSYT	4999	ARLYDAHWDYFDY	4229
162	GISLSTSGMG	4486	IWNNDN	5000	AWRPYYRYDSFAY	4230
18	GYTFTNYG	4487	INTYTGEP	5001	ARKYYDYEFAY	4231
85	GYTFTNYG	4488	INTYTGEP	5002	ARKYYDYEFAY	4232
163	GYTFTDYE	4489	IDPETGGT	5003	TRLGDYDVMDY	4233
86	GYTFTDYE	4490	IDPETGGT	5004	TRLGDYDVMDY	4234
164	GYTFTSYW	4491	IDPSDSYT	5005	ARAGRYGSSFDY	4235
165	GFSLSTSGMG	4492	IYWDDDK	5006	AGRPDDYDGAWFPY	4236
31	GYTFTSSW	4493	IHPNSGNT	5007	AIYYDYDAYYFDY	4237
87	GYTFTSSW	4494	IHPNSGNT	5008	AIYYDYDAYYFDY	4238
32	GYTFTSYW	4495	IHPNSGST	5009	ANPYYGYDVGY	4239
166	GYTFTDYV	4496	IYPGSGSN	5010	AREEKIYFDY	4240
88	GYTFTDYV	4497	IYPGSGSN	5011	AREEKIYFDY	4241
167	GYTFTSYW	4498	IHPNSGST	5012	ARYDGYWFDY	4242
168	GYTFTSYW	4499	IYPGNSDT	5013	TSLITTAYYFDY	4243
89	GYTFTSYW	4500	IYPGNSDT	5014	TSLITTAYYFDY	4244
169	GYTFTSYW	4501	IHPNSGST	5015	APETGDYGSSYVWYFDV	4245
170	GYTFTDYV	4502	IYPGSGST	5016	ARGKVTRFAY	4246
171	GFTFSSYA	4503	ISDGGSYT	5017	ARDQDSNWEYFDY	4247
172	GYTFTDYS	4504	INTETGEP	5018	ARESWDRAMDY	4248
19	GFTFSSYA	4505	ISSGGSYT	5019	ARHEEANWAWFAY	4249
90	GFTFSSYA	4506	ISSGGSYT	5020	ARHEEANWAWFAY	4250
173	GYSFTNYW	4507	IDPSDSET	5021	AIPYYAMDY	4251
91	GYSFTNYW	4508	IDPSDSET	5022	AIPYYAMDY	4252
174	GYTFTSSW	4509	IHPNSGNT	5023	ATYYGNYVWYFDV	4253
92	GYTFTSSW	4510	IHPNSGNT	5024	ATYYGNYVWYFDV	4254
175	GYTFTSYW	4511	IHPNSGST	5025	ASYGSSYWYFDV	4255
93	GYTFTSYW	4512	IHPNSGST	5026	ASYGSSYWYFDV	4256
20	GFSLTSYG	4513	IWSGGST	5027	ASYYGSSRSYWYLDV	4257
94	GFSLTSYG	4514	IWSGGST	5028	ASYYGSSRSYWYLDV	4258
176	GYTFTSYN	4515	LYSGNGDT	5029	ARDYYGSSHLWYFDV	4259
177	GFSLSTSGMG	4516	IYWDDDK	5030	ARRAHYDYGWYFDV	4260
178	GYTFTSYW	4517	IHPNSGST	5031	AGYDYDWYFDV	4261
33	GFTFSSYG	4518	ISSGGSYT	5032	TRHDDSSYDWFAY	4262
179	GFTFSSYG	4519	ISSGGSYT	5033	ARHEDSNYHYFDY	4263
34	GYTFTNYW	4520	IHPNSGTT	5034	ARFGDGYHFDY	4264
180	GFTFSSYG	4521	ISSGGSYT	5035	ARQNDSSWAWFAY	4265
95	GFTFSSYG	4522	ISSGGSYT	5036	ARQNDSSWAWFAY	4266
181	GYTFTSYW	4523	IHPNSGST	5037	ALPYSNYGWYFDV	4267
96	GYTFTSYW	4524	IHPNSGST	5038	ALPYSNYGWYFDV	4268
182	GYTFTSYW	4525	IDPSDSET	5039	ARDYYGSYWYFDV	4269
97	GYTFTSYW	4526	IDPSDSET	5040	ARDYYGSYWYFDV	4270
183	GFNIKDYY	4527	IDPEDGET	5041	AAYGNSAWFAY	4271
98	GFNIKDYY	4528	IDPEDGET	5042	AAYGNSAWFAY	4272
35	GYTFTNYG	4529	INTNTGEP	5043	ARWYPYFDY	4273
99	GYTFTNYG	4530	INTNTGEP	5044	ARWYPYFDY	4274
100	GYTFTNYG	4531	INTNTGEP	5045	ARWYPYFDY	4275
36	GYTFTSYW	4532	INPSSGYT	5046	ARSDGSSGNWYFDV	4276
101	GYTFTSYW	4533	INPSSGYT	5047	ARSDGSSGNWYFDV	4277
184	GFSLTSYG	4534	IWAGGST	5048	AREGGYTGYFDV	4278
102	GFSLTSYG	4535	IWAGGST	5049	AREGGYTGYFDV	4279
185	GYTFTSYW	4536	IDPSDSET	5050	AYSNYVPYYAMDY	4280
103	GYTFTSYW	4537	IDPSDSET	5051	AYSNYVPYYAMDY	4281
186	GYTFTDYV	4538	IYPGSGSA	5052	ARRGFDY	4282
21	GFTFSSYG	4539	ISSGGSYT	5053	ARHNYSNWDWFAY	4283
187	GYTFTSYW	4540	IHPNSGST	5054	ARDYYGSGYGYYFDY	4284
188	GYTFTSYW	4541	IHPNSGST	5055	ARDYYGSSYGWYFDV	4285
189	GYTFTSYW	4542	IHPNSGST	5056	ARDYYGSSYGWYFDV	4286
190	GYTFTSYW	4543	IHPNSGST	5057	ASDYYGSSYGWYFDV	4287
191	GYTFTSYW	4544	IHPNSGST	5058	ARDYYGSSYGWYFDV	4288
192	GYTFTSYW	4545	IHPNSGST	5059	TRDYYGSGYGWYFDV	4289
193	GYTFTNYW	4546	IDPSDSET	5060	ATYDGYYRFAY	4290
194	GYTFTNYW	4547	IDPSDSET	5061	ATYDVYYRFAY	4291
195	GYTFTSYW	4548	IHPNSGST	5062	ARDYGNYDYAMDY	4292
104	GYTFTSYW	4549	IHPNSGST	5063	ARDYGNYDYAMDY	4293
37	GYTFTSYW	4550	IHPNSGST	5064	ARDYGNYDYAMDY	4294
196	GYTFTSYW	4551	IHPNSGST	5065	ARDYGNYDYAMDY	4295
197	GFTFSSYG	4552	ISSGGSYT	5066	ASQLTGTWYYFDY	4296
198	GFTFSSYG	4553	ISSGGSYT	5067	ASQLTGTWYYFDY	4297
199	GFTFSSYG	4554	ISSGGSYT	5068	ASQLTGTWYYFDY	4298
22	GFNIKDTS	4555	IDPANGNT	5069	ARGPDDGYFYYYSMDY	4299
200	GFTFSNYY	4556	INSNGGST	5070	ARQEGIGYAMDY	4300
201	GYTFTEYT	4557	IYPNNGGT	5071	ARGGWLLGY	4301
202	GFSLTSYG	4558	IWSGGST	5072	ARDGGIRGAMDY	4302
203	GYTFSSYW	4559	ILPGSGST	5073	ARRGYGYDEGFDY	4303
204	GYTFTDYE	4560	IDPETGGT	5074	TRNYDYAMDY	4304
205	GFTFSSYY	4561	INSNGGST	5075	ARQEGIGYALDY	4305
206	GFTFSSYA	4562	ISSGGST	5076	AREREWGVYYGSSLDY	4306
207	GFNIKDTY	4563	IDPANGNT	5077	ARSDGNYD	4307
208	GFTFSNYY	4564	INSNGGST	5078	ARQEGIGYGMDY	4308
209	GFTFNTYV	4565	IRSKSDNYAT	5079	VRHDGVVGFDV	4309
210	GYSITSGYY	4566	ISYDGSN	5080	ARGGGRG	4310
211	GYTFTDYS	4567	INTETGEP	5081	ARDYYDYYYAMDY	4311
212	GYTFTDYS	4568	INTETGEP	5082	ARESWDRAMDY	4312
213	GYTFTNYW	4569	IDPYDSET	5083	ARIYSDYDGAWFAY	4313
214	GYTFTDYY	4570	VNPYNGGT	5084	ARGTVGFAY	4314
215	GFTFSSYA	4571	ISSGGST	5085	AREREWGVFYGSSLDY	4315
216	GFTFSSYA	4572	ISSGGSYT	5086	ARHDDSSYGYFDY	4316
217	GFTFSNYA	4573	ISSGGTT	5087	ARTMPDV	4317
218	GFSLTSYG	4574	IWAGGST	5088	ARDTDGYYWAMDY	4318
219	GYSITSDHA	4575	ISYSGST	5089	ARKWGDY	4319
220	GYTFTDYE	4576	IDPETGGT	5090	TRNYDYALDY	4320
221	GYSITSGYY	4577	ISYDGSN	5091	ARGGGRG	4321
222	GFTFSNYY	4578	INSNGGST	5092	ARQEEIGYAMDY	4322
223	GFNIKDYF	4579	IDPETDNT	5093	ARSGNMGFTY	4323
105	GFNIKDYF	4580	IDPETDNT	5094	ARSGNMGFTY	4324
224	GFTFSSYA	4581	ISSGGSYT	5095	ASQGGSSWGAMDY	4325
106	GFTFSSYA	4582	ISSGGSYT	5096	ASQGGSSWGAMDY	4326
225	GFTFSSYA	4583	ISNGGSYT	5097	ARHEITTRFAY	4327
226	GYSITSGYY	4584	MSYDGSN	5098	AREAGYFDY	4328
227	GFSFNTYA	4585	IRSKSNNYAT	5099	VRQYGYDFDY	4329
228	GFTFSSYG	4586	ISSGGSYT	5100	ARHKGVNWDYFDY	4330
229	GYTFTDYE	4587	IDPETGGT	5101	TRGDGNYDSWYFDV	4331
230	GFTFSSYA	4588	ISSGGSYT	5102	ARLPVTTVVFDY	4332
231	GFTFSSYA	4589	ISSGGSYT	5103	ARRPVVVPFDY	4333
232	GFSLTSYG	4590	IWSGGST	5104	ARGWDADYFDY	4334
233	GYTFTNYW	4591	IHPNSGST	5105	TRYDYDDY	4335
234	GYTFTDYY	4592	INPNNGGT	5106	ARSELGLYAMDY	4336
235	GYTFTGYW	4593	ILPGSGST	5107	ARGRIHYFDY	4337
236	GYTFTGYW	4594	ILPGSGST	5108	ARGRIHYFDY	4338
237	GFSLTSYG	4595	IWSGGST	5109	ARKGYGYDWYFDV	4339
107	GFSLTSYG	4596	IWSGGST	5110	ARKGYGYDWYFDV	4340
238	GYTFTSYW	4597	IDPSDSYT	5111	ARSSYYYYAMDY	4341
108	GYTFTSYW	4598	IDPSDSYT	5112	ARSSYYYYAMDY	4342
239	GYSITSGYY	4599	ISYDGSN	5113	ARGGGRD	4343
240	GFSLTSYG	4600	IWSGGST	5114	ARGGDYDSYAMDY	4344
241	GYTFTSYW	4601	IYPGSGST	5115	ARESVYDGYSWYFDV	4345
242	GYSFTDYN	4602	INPNYGTT	5116	ASTYDYDDWYFDV	4346
243	GYTFTSYW	4603	IDPSDSYT	5117	ARSGNYLYAMDY	4347
244	GYSFTDYN	4604	INPNYGTT	5118	AREGTSWYFDV	4348
245	GFSLTSYG	4605	IWRGGST	5119	AKKGDGYDWYFDV	4349
246	GFSLTSYG	4606	IWSGGST	5120	AREGNYGSSYDAMDY	4350
247	GYTFTSYW	4607	IDPSDSYT	5121	ARSSNYPYAMDY	4351
248	GFNIKNTY	4608	IDPANGNT	5122	AYYSGLY	4352
249	GYTFTSYW	4609	IDPSDSET	5123	ARRGQIYYGYSWFAY	4353
250	GYTFTDYY	4610	INPNNGGT	5124	ARSTVVADWYFDV	4354
251	GYTFTSYG	4611	IYPRSGNT	5125	ARSGSSYGYFDV	4355
252	GFSLTSYG	4612	IWSGGST	5126	ARKGGYDAYAMDY	4356
253	GYSFTDYN	4613	INPNYGTT	5127	AREGFITTVVAVDY	4357
254	GYTFTDYE	4614	IDPETGGT	5128	TREGNYDAMDY	4358
255	GYTFTSYW	4615	IDPSDSYT	5129	ARWDYYGVDY	4359
256	GFTFSGYW	4616	ISPGGGST	5130	ASSLTATHTYEYDY	4360

LCDR1

LCDR2

LCDR3

97	QGISNY	8066	YTS		QQYSKLPYT	6829
182	QGISNY	8067	YTS		QQYSKLPYT	6828
86	QDISNY	8068	YTS		QQDNTLPRT	6793
96	QDISNY	8069	YTS		QQGNTLPFT	6827
151	QDISNY	8070	STS		QQGNTLPWT	6768
152	QDISNY	8071	STS		QQGNALPWT	6769
153	QDISNY	8072	STS		QQGNTLPWT	6770
163	QDISNY	8073	YTS		QQDNTLPRT	6792
164	QDISNY	8074	YTS		QQGNTLPWT	6794
181	QDISNY	8075	YTS		QQGNTLPFT	6826
202	QSIVHSNGNTY	8076	KVS		FQGSHVPWT	6861
206	QSIVYSNGNTY	8077	KVS		FQGSHVPPT	6865
215	QSIVHSNGNTY	8078	KVS		FQGSHVPPT	6874
242	QSIVHSNGDTY	8079	KVS		FQGSHVPLT	6905
204	QSLLDSDGKTY	8080	LVS		WQGTHFPWT	6863
214	QSLLDSDGKTY	8081	LVS		WQGTHFPWT	6873
220	QSLLDSDGKTY	8082	LVS		WQGTHFPWT	6879
229	QSLLDSDGKTY	8083	LVS		WQGTHFPWT	6890
235	QSLLDSDGKTY	8084	LVS		WQGTHFPFT	6896
162	ENIYYS	8085	NAN		KQAYDVPYT	6789
101	GNIHNY	8086	NAK		QHFWSTPWT	6836
36	GNIHNY	8087	NAK		QHFWSTPWT	6835
188	GNIHNY	8088	NAK		QHFWSTPWT	6844
172	ENIYSY	8089	NAK		QHFWGTPYT	6807
189	ENIYSY	8090	NAK		QHHYGTPFT	6845
249	ENIYSY	8091	NAK		QHHYGTPYT	6912
250	ENIYSY	8092	NAK		QHHYGTPPT	6913
57	DNIYSN	8093	AAT		QHFWGTPWT	6712
58	ENIYSN	8094	AAT		QHFWGTPWT	6713
3	ENIYSN	8095	AAT		QHFWGTPWT	6701
4	ENIYSN	8096	AAT		QHFWGTPWT	6702
5	ENIYSN	8097	AAT		QHFWGSPWT	6703
6	ENIYSN	8098	AAT		QHFWGTPWT	6704
7	ENIYSN	8099	AAT		QHFWGTPWT	6705
8	ENIYSN	8100	AAT		QHFWGTPWT	6706
9	DNIYSN	8101	AAT		QHFWGTPWT	6707
10	ENIYSN	8102	AAT		QHFWGTPWT	6708
11	ENIYSN	8103	AAT		QHFWGTPWT	6709
12	ENIYSN	8104	AAT		QHFWGTPWT	6710
13	ENIYSN	8105	AAT		QHFWGSPWT	6711
17	ENIYSN	8106	AAT		QHFWGTPWT	6777
165	ENIYSN	8107	AAT		QHFWGTPWT	6795
179	ENIYSN	8108	AAT		QHFWGTPYT	6822
194	ENIYSN	8109	AAT		QHFWGTPFT	6850
37	ENIYSN	8110	AAT		QHFWGTPYT	6853
207	ENIYNN	8111	AAT		QHFWGTPWT	6866
212	ENIYSN	8112	AAT		QHFWGTPWT	6871
248	DHINNW	8113	GAT		QQYWSTPLT	6911
38	QDINSY	8114	RAN		LQYDEFPLT	6682
39	QDINGY	8115	RAN		LQYDEFPPT	6683
40	QDINSY	8116	RAK		LQYDEFPPT	6684
41	QDINGY	8117	RAN		LQYDEFPPT	6685
42	QDINSY	8118	RAK		LQYDEFPPT	6686
43	QDINSY	8119	RAN		LHYDEFPPT	6687
44	QDINSY	8120	RAN		LQYDEFPPT	6688
45	QDINSY	8121	RAN		LQYDEFPPT	6689
46	QDINSY	8122	RAN		LQYDEFPPT	6690
47	QDINSY	8123	RAN		LQYDEFPPT	6691
48	QDINSY	8124	RAN		LQYDEFPPT	6692
49	QDINSY	8125	RAN		LQYDEFPPT	6693
50	QDINSY	8126	RAN		LQYDEFPPT	6694
51	QDINSY	8127	RAN		LQYDEFPPT	6695
52	QDINSY	8128	RAN		LQYDEFPPT	6696
53	QDINSY	8129	RAN		LQYDEFPPT	6697
54	QDINSY	8130	RAN		LQYDEFPPT	6698
55	QDINSY	8131	RAN		LQYDEFPPT	6699
56	QDINSY	8132	RAN		LQYDEFPPT	6700
91	QDINSY	8133	RAN		LQYDEFPLT	6811
109	QDINSY	8134	RAN		LHYDEFPPT	6664
110	QDINSY	8135	RAN		LQYDEFPPT	6665
111	QDINSY	8136	RAN		LQYDEFPPT	6666
112	QDINSY	8137	RAN		LQYDEFPPT	6667
1	QDINSY	8138	RAN		LQYDEFPPT	6668
113	QDINSY	8139	RAN		PQYVESPPT	6669
114	QDINSY	8140	RAN		LQYDEFPPT	6670
115	QDINSY	8141	RAN		LQYDEFPPT	6671
23	QDINSY	8142	RAN		LQYDEFPPT	6672
116	QDINSY	8143	RAN		LQYDEFPPT	6673
117	QDINSY	8144	RAN		LQYDEFPLT	6674
2	QDINSY	8145	RAN		LQYDEFPPT	6675
118	QDINGY	8146	RAN		LQYDEFPPT	6676
119	QDINSY	8147	RAN		LQYDEFPPT	6677
120	QDINSY	8148	RAN		LQYDEFPPT	6678
121	QDINSY	8149	RAN		LQYDEFPPT	6679
122	QDINSY	8150	RAN		LQYDEFPPT	6680
123	QDINSY	8151	RAK		LQYDEFPPT	6681
124	QDINSY	8152	RAN		LQYDEFPPT	6714
173	QDINSY	8153	RAN		LQYDEFPLT	6810
193	QDINSY	8154	RAN		LQYDEFPPT	6849
203	QDINSY	8155	RAN		LQYDEFPPT	6862
70	QDIVKN	8156	YAT		LQFYEFPLT	6749
87	QDIVKN	8157	YAT		LQFYEFPYT	6797
89	QDIVKN	8158	YAT		LQFYEFPLT	6803
99	QDIVKN	8159	YAT		LQFYEFPYT	6833
100	QDIVKN	8160	YAT		LQFYEFPYT	6834
16	QDIVKN	8161	YAT		LQFYEFPLT	6745
141	QDIVKN	8162	YAT		LQFYEFPLT	6746
142	QDIVKN	8163	YAT		LQFYEFPLT	6747
143	QDIVKN	8164	YAT		LQFYEFPLT	6748
31	QDIVKN	8165	YAT		LQFYEFPYT	6796
168	QDIVKN	8166	YAT		LQFYEFPLT	6802
35	QDIVKN	8167	YAT		LQFYEFPYT	6832
239	QDIVKN	8168	YAT		LQFYEFPLT	6902
21	QNINVW	8169	KAS		QQGQSYPLT	6842
218	QNINVW	8170	KAS		QQGQSYPYT	6877
106	TDIDDD	8171	EGN		LQSDNLPLT	6885
197	TDIDDD	8172	EGN		LQSDNLPLT	6855
22	TDIDDD	8173	EGN		LQSDNLPLT	6858
224	TDIDDD	8174	EGN		LQSDNLPLT	6884
95	TDIDDD	8175	EGN		LQSDNMPLT	6825
157	TDIDDD	8176	EGN		LQSDNMPFT	6778
27	IDIDDD	8177	EGN		LQSDNMPFT	6779
33	TDIDDD	8178	EGN		LQSDNMPLM	6821
180	TDIDDD	8179	EGN		LQSDNMPLT	6824
216	TDIDDD	8180	EGN		LQSDNMPLT	6875
228	TDIDDD	8181	EGN		LQSDNMPLT	6889
24	QDINKY	8182	YTS		LQYDNLMYT	6742
139	QDINKY	8183	YTS		LQYDILMYT	6743
140	QDINKY	8184	YTS		LQYDILMYT	6744
217	QDINKY	8185	YTS		LQYDNLYMYT	7780
230	QDINKY	8186	YTS		LQYDNLRT	7781
240	ESVDNYGISF	8187	AAS		QQSKEVPPT	6903
252	ESVDNYGISF	8188	AAS		QQSKEVPPT	6915
66	QSVDYDGDSY	8189	AAS		QQSNEDPLT	6738
67	QSVDYDGDSY	8190	AAS		QQSNEDPLT	6739
68	QSVDYDGDSY	8191	AAS		QQSNEDPLT	6740
69	QSVDYDGDSY	8192	AAS		QQSNEDPLT	6741
71	QSVDYDGDSY	8193	AAS		QQSNKDPLT	6756
72	QSVDYDGDSY	8194	AAS		QQSNKDPLT	6757
73	QSVDYDGDSY	8195	AAS		QQSNEDPLT	6758
74	QSVDYDGDSY	8196	AAS		QQSNKDPFT	6759
75	QSVDYDGDSY	8197	AAS		QQSNKDPFT	6760
76	QSVDYDGDSY	8198	AAS		QQSNKDPFT	6761
83	QSVDYDGDSY	8199	AAS		QQSNEDPLT	6782
88	QSVDYDGDSY	8200	AAS		QQSNEDPWT	6800
135	QSVDYDGDSY	8201	AAS		QQSNEDPLT	6733
136	QSVDYDGDSY	8202	AAS		QQSNEDPLT	6734
137	QSVDYDGDSY	8203	AAS		QQSNEDPLT	6735
138	QSVDYDGDSY	8204	AAS		QQSNEDPLT	6736
15	QSVDYDGDSY	8205	AAS		QQSNEDPLT	6737
146	QSVDYDGDSY	8206	AAS		QQSNKDPLT	6753
147	QSVDYDGDSY	8207	AAS		QQSNEDPLT	6754
148	QSVDYDGDSY	8208	AAS		QQSNKDPFT	6755
159	QSVDYDGDSY	8209	AAS		QQSNEDPLT	6781
161	QSVDYDGDSY	8210	AAS		QQSNEDPPT	6787
166	QSVDYDGDSY	8211	AAS		QQSNEDPWT	6799
170	QSVDYDGDSY	8212	AAS		QQSNEDPPT	6805
177	QSVDYDGDSY	8213	VAS		QQSHEDPRT	6819
186	QSVDYDGDSY	8214	AAS		QQSNEDPLPT	7776
225	QSVDYDGDSY	8215	AAS		QQSNEDPWT	6886
236	QSVDYDGDSY	8216	AAS		QQSNEDPFT	6897
233	ETVDSYGYSF	8217	RAS		QQSNEDPRT	6894
77	QSVSTSSYSY	8218	YAS		QHSWEIPLT	6765
78	QSVSTSSYSY	8219	YAS		QHSWEIPLT	6766
79	QSVSTSSYSY	8220	YAS		QHSWEIPLT	6767
149	QSVSTSSYSY	8221	YAS		QHSWEIPLT	6762
150	QSVSTSSYSY	8222	YAS		QHSWEIPLT	6763
26	QSVSTSSYSY	8223	YAS		QHSWEIPLT	6764
246	QSVSTSSYSY	8224	YAS		QHSWEIPLT	6909
105	SSVNY	8225	YTS		QQFTSSPST	6883
25	SSVNY	8226	YTS		QQFTSSHT	7768
144	SSVNY	8227	YTS		QQFTSSHT	7769
145	SSVNY	8228	YTS		QQFTSSHT	7770
190	SSVNY	8229	YTS		QQFTSSLT	7777
223	SSVNY	8230	YTS		QQFTSSPST	6882
32	SSVSY	8231	DTS		QQWSSYPLT	6798
209	SSVSY	8232	DTS		QQWSTYPPIT	7779
210	SSVSY	8233	DTS		QQWSSYPFT	6869
221	LSVSD	8234	DTS		QQWSSYPFT	6880
90	SSVSY	8235	STS		QQRSSFPYT	6809
19	SSVSY	8236	STS		QQRSSFPYT	6808
34	SSVSY	8237	STS		QQRSTYPT	7775
198	SSVSY	8238	STS		QQRSSYPPT	6856
64	SSVSY	8239	DTS		QQWSSNPLY	6731
65	SSVSY	8240	DTS		QQWSSNPLY	6732
	SSVSY	8241	DTS		QQWSSNPLT	6901
131	SSVSY	8242	DTS		QQWSSNPLYT	7763
132	SSVSY	8243	DTS		QQWSSNPHVHV	7764
133	SSVSY	8244	DTS		QQWSSNPLYT	7765
14	SSVSY	8245	DTS		QQWSSNPLYT	7766
134	SSVSY	8246	DTS		QQWSSNPLYT	7767
187	SSVSY	8247	DTS		QQWSSNPLT	6843
199	SSVSY	8248	DTS		QQWSSNPLT	6857
238	SSVSY	8249	DTS		QQWSSNPLT	6900
243	SSVSY	8250	DTS		QQWSSNPLT	6906
247	SSVSY	8251	DTS		QQWSSNPLT	6910
251	SSVSY	8252	DTS		QQWSSNPPT	6914
178	SSVSY	8253	DTS		FQGSGYPLT	6820
219	SSVSY	8254	LTS		QQWSSNPPT	6878
255	SSISY	8255	DTS		HQRSSYPT	7785
211	SSVSY	8256	ATS		QQWSSNPYT	6870
200	SSVSSSY	8257	STS		HQWSSYPPT	6859
205	SSVSSSY	8258	STS		HQWSSYPPT	6864
208	SSVSSSY	8259	STS		HQWSSYPPT	6867
222	SSVSSSY	8260	STS		HQWSSYPPT	6881
227	SSVSSSY	8261	STS		HQWSSYPPT	6888
98	QSISDY	8262	YAS		QNGHSFPWT	6831
104	QSISDY	8263	YAS		QNGHSFPYT	6852
183	QSISDY	8264	YAS		QNGHSFPWT	6830
195	QSISDY	8265	YAS		QNGHSFPYT	6851
241	QSISDY	8266	YAS		QNGHSFPLT	6904
226	QSISNN	8267	YAS		QQSNSWPFT	6887
60	ENVVTY	8268	GAS		GQSYSYPFT	6722
61	ENVVTY	8269	GAS		GQSYSYPFT	6723
62	ENVVTY	8270	GAS		GQSYSYPFT	6724
63	ENVVTY	8271	GAS		GQSYSYPFT	6725
59	QDINSY	8272	RAN		LQYDEFPPT	6721
125	ENVVTY	8273	GAS		GQSYSYPFT	6715
126	ENVVTY	8274	GAS		GQSYSYPFT	6716
127	ENVVTY	8275	GAS		GQSYSYPFT	6717
128	ENVVTY	8276	GAS		GQSYSYPFT	6718
129	ENVVTY	8277	GAS		GQSYSYLIHVR	7761
130	ENVVTY	8278	GAS		GQSYSYLIHVR	7762
232	ENVGTY	8279	GAS		GQSYSYPPT	6893
93	QDVGTA	8280	WAS		QQYSSYPFT	6815
175	QDVGTA	8281	WAS		QQYSSYPFT	6814
192	QDVGTA	8282	WAS		QQYSSYPFT	6848
213	QDVSTA	8283	WAS		QQHYSTPWT	6872
94	QSVSND	8284	YAS		QQDYTSLPT	6817
20	QSVSND	8285	YAS		QQDYTSLPT	6816
244	ESLYSSKHKVHY	8286	GAS		AQFYSYPYT	6907
253	ESLYSSKHKVHY	8287	GAS		AQFYSYPYT	6916
85	QSLLNSSNQKNY	8288	FAS		QQHYSTPLT	6791
18	QSLLNSSNQKNY	8289	FAS		QQHYSTPLT	6790
160	QSLLYSTNQKNY	8290	WAS		QQYYSYPPWT	7772
234	QSLLYSTNQKNY	8291	WAS		QQYYSYRT	7782
171	QDIGIS	8292	ATS		LQYASSPYT	6806
92	QDIHGY	8293	ETS		LQYASSPLT	6813
103	QEISGY	8294	AAS		LQYASYPWT	6840
174	QDIHGY	8295	ETS		LQYASSPLT	6812
185	QEISGY	8296	AAS		LQYASYPWT	6839
29	TGAVTTSNY	8297	GTN		ALWYSNHL	7773
30	TGAVTTSNY	8298	GTN		ALWYSNHWV	6788
167	TGAVTTSNY	8299	GTN		ALWYSNHWV	6801
176	TGAVTTSNY	8300	GTN		ALWYSNHLV	6818
191	TGAVTTSNY	8301	STN		TLWYSNHWV	6847
196	TGAVTTSNY	8302	GTN		ALWYSNHWV	6854
231	TGAVTTSNY	8303	GTN		VLWYSNHLV	6892
80	TGAVTTSNY	8304	GTS		ALWYSTHYV	6774
81	TGAVTTSNY	8305	GTS		ALWYSTHYV	6775
82	TGAVTTSNY	8306	GTS		ALWYSTHYV	6776
84	TGAVTTSNY	8307	GTS		ALWYSTHWV	6785
102	TGAVTTSNY	8308	GTS		ALWYSTHYV	6838
154	TGAVTTSNY	8309	GTS		ALWYSTHYV	6771
155	TGAVTTSNY	8310	GTS		ALWYSTHYV	6772
156	TGAVTTSNY	8311	GTS		ALWYSTHYV	6773
158	TGAVTTSNY	8312	GTS		ALWYSTHY	7771
28	TGAVTTSNY	8313	GTS		ALWYSTHWV	6784
184	TGAVTTSNY	8314	GTS		ALWYSTHYV	6837
254	TGAVTTSNY	8315	GTS		ALWYSTHYV	6917
107	SQHSTYT	8316	LKKDGSH	8826	GVGDTIKEQFVYV	6899
169	SQHSTYT	8317	LKKDGSH	8827	GVGDTIKEQFVFV	7774
201	SQHSTYT	8318	LKKDGSH	8828	GVGDTIKEQFVYV	7778
237	SQHSTYT	8319	LKKDGSH	8829	GVGDTIKEQFVYV	7783
245	SQHSTYT	8320	LKKDGSH	8830	GVGDTIKEQFVYV	7784

HCDR1

HCDR2

HCDR3

265	GGTFSSYA	11540	INPSGGT	11802	ARDLGDPGMDV	11409
266	GGTFSNYA	11541	IDPSGGST	11803	ARDLGDMGMDV	11410
267	GGTFSNYA	11542	INPSGGST	11804	ARDVGDRGMDV	11411
263	GGTFSSYA	11543	INPSGGT	11805	ARDLGDPGMDV	11412
268	GSTFSGYY	11544	IDPNGGGT	11806	AKDIVHDGTEYFQH	11413
269	GYTFTSYY	11545	INPSGGST	11807	AKDIVHDGTEYFQH	11414
270	GGTFSSYA	11546	INPSGGST	11808	AREGRDHDAFDI	11415
271	GFTFTDYG	11547	INPSGGST	11809	AREGRSHDAFDI	11416
272	GYTFTGYY	11548	MNPHSGDT	11810	ARWVGTTEYYYYYYMDV	11417
273	GYTFTDYY	11549	IDPSGGST	11811	ATTAYYDFWSGYSMDV	11418
274	GYTFTSHY	11550	IDPSGGST	11812	ARDMDNWNTGYYYYMDV	11419
275	GGTFSSYA	11551	VNPNSGDT	11813	ARDQRGGDAWDV	11420
276	GGTFSNYA	11552	ITPSGGST	11814	ARDTAGHFDI	11421
277	GGTFRNDV	11553	MNPNSGNT	11815	ARDNPDLDGMDV	11422
278	GGTFSSYA	11554	ISAYNGNT	11816	ARDLVGHFDY	11423
279	GGTFSSYA	11555	INPNSGGT	11817	ARDGYSGSYSD	11424
264	GGTFSSYA	11556	INPNSGGT	11818	ARDGYSGSYSD	11425
257	GGTFSSYA	11557	INPNSGGT	11819	ARDGYSGSYSD	11426
280	GNTLSSHA	11558	INPSGGST	11820	ARDQGSSGTFDY	11427
281	GGTLSSYA	11559	INPNSGGT	11821	ARDSTDVIDY	11428
282	GYIFTSYD	11560	INPNSGDT	11822	ARDGGTVTPTEEYYYYG-	11429
					MDV
283	GGTFSSYA	11561	ISVYNGNT	11823	ASLDDLDY	11430
284	GHTFTSYY	11562	INPNNGGT	11824	ARDMVRDSAEYFQH	11431
285	GYTFITSY	11563	INPSGGTT	11825	ARDSSGYPIDY	11432
286	GYTFTSYD	11564	IIPLSGAP	11826	ARGALYNWNDGWFDP	11433
258	GYTFTSYD	11565	IIPLSGAP	11827	ARGALYNWNDGWFDP	11434
287	GFTVGSWY	11566	IWYEGSNK	11828	ARLGTASLPYFDY	11435
288	GYTFTGYY	11567	INPNRGDT	11829	ARESGDGFDP	11436
289	GYTFTNYY	11568	MNPNSGNT	11830	ARDWPNWFDP	11437
290	GYSFTDNY	11569	IRSDNGET	11831	AREVQLVGFDY	11438
291	GYTFSDHH	11570	IIPIFGTA	11832	ARGSSWYLHFQH	11439
260	GYTFSDHH	11571	IIPIFGTA	11833	ARGSSWYLHFQH	11440
292	GGTFSSYA	11572	IIPIFGTT	11834	AKGVDRYNWNDAFDY	11441
293	GYTFTDYY	11573	IHSNSGGT	11835	ARESSGYDSSLDY	11442
294	GGTFSSYG	11574	INPNSGDT	11836	TTDPRLDSSDPGY	11443
295	GGTFGNYG	11575	ISAYNGNT	11837	ARGGMDV	11444
296	GGTFSRYG	11576	SYPSDGST	11838	ARDRLGDLDY	11445
261	GGTFSRYG	11577	SYPSDGST	11839	ARDRLGDLDY	11446
297	GGTFSSYA	11578	MNPNSGNT	11840	ARDSIVGGYPFDY	11447
298	GYTFTSYD	11579	ITPIFGTT	11841	AREGYSSSWHDDAFDI	11448
299	GGTFSNYA	11580	IDPSGGST	11842	ARDLGDYGLDS	11449
300	GYTFTGYY	11581	MNPNSGDT	11843	ATGGSDSSGYYYEGYFQH	11450
301	GGTFSSYA	11582	MSPNSGNT	11844	ARDKGGYYDSSGYYWY	11451
302	GFSLSSYE	11583	ISSNGGST	11845	ARVGDGDGYNPDFDY	11452
303	GYTFTSYG	11584	IDPTSGAT	11846	AKDPIVATEVDY	11453
304	GGTFSSYA	11585	MSPNSGNT	11847	ARDSGAFDI	11454
305	GVTISNYA	11586	MNPNSGNT	11848	AREGLLDAFDI	11455
306	GGTFSRYG	11587	MNPYDGNT	11849	ARGGRHHDAFDI	11456
307	GGTFSSYA	11588	INPSGDGT	11850	ARDISNDAFDI	11457
308	GYILTGHY	11589	ISAYNGDT	11851	ARGSSWDDAFDI	11458
309	GFTFSNHY	11590	IGAGGGT	11852	AREGWNDDVFDI	11459
310	GGTFSSYA	11591	INPSAGTT	11853	ARDGNFGAFDI	11460
311	GYSFTTYA	11592	IIPIFGTA	11854	ARDKSGWNYGSGSYN-	11461
					DAFDI
312	GYAFTGYY	11593	MNPNSGKT	11855	ARDGGLDFDY	11462
313	GYTFTTYY	11594	MNPNTGDT	11856	AKDPAVTPDAFDI	11463
314	GGTLSSYA	11595	IDPSGGGT	11857	AGSLYYYGMDV	11464
315	GGTFGSSA	11596	IIPIFGTA	11858	AKEDDILPPRAFDI	11465
316	GFTFDDYA	11597	ISGGGGVT	11859	ARVYSSGWLDAFDI	11466
317	GGTFSSYA	11598	ISGYNGNT	11860	ASSDVSPDAFDI	11467
318	GGTQNIYA	11599	VNPNSGNT	11861	ATPTSSSDDAFDI	11468
319	GGTFSSYA	11600	INPNSGGT	11862	ARASRGDDAFDI	11469
320	GIPFTSDD	11601	INPSGGST	11863	ARERYEGGY-	11470
					SSGPGNYYYGMDV
321	GGTFSNYA	11602	MNPNSGNT	11864	ARDDDYGDYPV	11471
322	GDTFSDHA	11603	MNPKIGNT	11865	VYDSSGYDAFDI	11472
323	GYTFTSYD	11604	INPGTGGT	11866	ARETPSDYYDSSGYYYN-	11473
					DAFDI
324	GGTFSSYA	11605	IPSGGT	11867	ARDLGTTFDI	11474
325	GYTFTAYY	11606	INPDNDNA	11868	AKDIAVAALAYGMDV	11475
326	GFTFSSYA	11607	ISYDGSDQ	11869	ARQSLYYYYGMDV	11476
327	GYTFTDYY	11608	ISTFTGNT	11870	ARDAPLAAAGTDYYYG-	11477
					MDV
262	GYTFTDYY	11609	ISTFTGNT	11871	ARDAPLAAAGTDYYYG-	11478
					MDV
328	GFTFSSYA	11610	ISDDGITK	11872	ARDDSSGYGGMDV	11479
329	GFTFSSYA	11611	ISYDGGDK	11873	ASGSLVLGYYYMDV	11480
330	GYTFTNYY	11612	INPNTGGT	11874	ATGGGGSYYDAFDV	11481
331	GGTFSSYA	11613	INPNSGNT	11875	ARDIGEGYSMDV	11482
332	GFTFSNHY	11614	ISYDGSNK	11876	AREEKYSSSWYVGVDAFDI	11483
333	GFTFSSSA	11615	ISGSGDNA	11877	ARDQEDYYYDSSGYGMDV	11484
334	GGTFSSHA	11616	IIPIFGTA	11878	AKGDWGIVVVPAAIGAFDI	11485
335	GYTFTAYY	11617	ISPVFGST	11879	ARDLGYYDSSGYRYDAFDI	11486
336	GYTFTSYD	11618	ISPMFGTA	11880	AKDGWYYGMDV	11487
337	GGTFSSYG	11619	INPNSGGT	11881	ARGEAGNLDWYFDL	11488
338	GGTFSNYG	11620	INPNNGDT	11882	AREDVWYFDL	11489
339	GYTFTTYG	11621	ISTYDGKT	11883	ALHLGGDWYFDL	11490
340	GYTFTGYY	11622	INPNTGAT	11884	ARQHGDYDWYFDL	11491
341	GDTFTTYY	11623	INPNSGNT	11885	ARDSGRH	11492
342	GGTFSSYG	11624	IIPMLGIA	11886	VREEVAGANWFDP	11493
343	GYTFTSYA	11625	INPSGGST	11887	AREGDYGSGEFDY	11494
344	GYTFTSSY	11626	MNPRSGNT	11888	ARERDDYGDYGWLDY	11495
345	GYTFTGYY	11627	INPSGGST	11889	ARDLYDSSGY-	11496
					WHYYYYMDV
346	GGTFSSYA	11628	INPNSGGT	11890	ARFSGYDYVDY	11497
347	GGTFSSYA	11629	INPNGGNT	11891	ARDVGEDFDL	11498
348	GYTFTSYY	11630	INPADGDT	11892	ARDFDWLFAMDV	11499
349	GGTFSNYA	11631	INPNGGTT	11893	AKHGDHGFYV	11500
350	GGTFSSYA	11632	INPNVGSA	11894	AREDSGTSWFDP	11501
351	GYTFTSYY	11633	INPSDGST	11895	ARDDRGSNYYYGMDV	11502
352	GYTFTAYY	11634	MNPNSGTT	11896	ARDSSDYYGDYRADAFDI	11503
353	GYTFTSYD	11635	ISPSGDAT	11897	VKGLDH	11504
354	GFSFSDYG	11636	IGGIGDST	11898	ARMNYGDSNYYYYYG-	11505
					MDV
355	GYTFTSYD	11637	ISPSDGST	11899	ARGAVGFDY	11506
356	GYTFTSYG	11638	INTYSGYT	11900	TTDDFLSFGY	11507
357	GYMFTDYY	11639	IIPYFGTA	11901	ARSISGSYVLDAFDI	11508
358	GYTFNSYG	11640	IIPIFGTA	11902	ARDWGYGDYADDAFDI	11509
359	GGTFSNND	11641	INPIYGSA	11903	AADWRGFDY	11510
360	GYTFTEYA	11642	MNPHNGDT	11904	AREGDYLGYPIDC	11511
361	GFTFSDYS	11643	IWQDGNVK	11905	ARDGNSGYVF	11512
362	GYTFTTYY	11644	INPNTGDT	11906	ARTAEAVAGLPAFDY	11513
363	GGTSNNYA	11645	IIPLFGTT	11907	ARVTLYGDYDY	11514
364	GYSLITHW	11646	INPSDGVT	11908	AREYYGEGFDY	11515
259	GYSLITHW	11647	INPSDGVT	11909	AREYYGEGFDY	11516
365	GGTFSSYA	11648	INPSGGST	11910	ARDLGDTAMDG	11517
366	GYTFTSYY	11649	ITPSGGST	11911	ARDGGLASFDY	11518
367	GGTFSSYA	11650	MNPNSGNT	11912	ARGGGWAMTDAFDI	11519
368	GFTFDDYG	11651	IYSGGDT	11913	TRKEYYYDSSGYLRLFDY	11520
369	GYTFTDYY	11652	INPIFGTS	11914	ARDISGYDYYYYGMDV	11521
370	GGTLNNYA	11653	IDPSDGTI	11915	ARSDYDFWSGLGGYFDY	11522
371	GGTFSSYA	11654	IDPNSGGT	11916	ARDSAEWELGGSFDY	11523
372	GFTFSNHY	11655	IGVNGDT	11917	AREGLVFSGRGHWYFDL	11524
373	GGTFSNYA	11656	INPNGGNT	11918	ARDYEDADFDG	11525
374	GYTFSDHH	11657	MNPDSGNT	11919	ARDSTSGVDY	11526
375	GFTFSSYA	11658	ISYDGHDQ	11920	ARGEQQLEGFYYYYGMDV	11527
376	GFTFSSYW	11659	ISYDGSKE	11921	ASDYGDYGTYDY	11528
377	GFTFSSYW	11660	ISGGGDDT	11922	AREPLAYCGGDCPGGFDY	11529
378	GFTFSDHY	11661	IGTGGDT	11923	ARHEDTAIFLDY	11530
379	GYTFTSYY	11662	ISPSDGST	11924	ARDGYDAWSYGMDV	11531
380	GYTFTGYY	11663	MNPNSGNT	11925	ARDGVTGTDY	11532
381	GFAFSSYV	11664	ISGAGDST	11926	AREPTTVTDDWYFDL	11533
382	GFAFSSHW	11665	ISGNGDNS	11927	ARDRAPEYFDL	11534
383	GGTFSSYA	11666	INPNSGGT	11928	ARDDYGDYGGGMDV	11535
384	GYTFTDYY	11667	MNPNSGHT	11929	AKDTSPRYGDGFFDY	11536
385	GFTFSSYW	11668	TSYDGSNK	11930	ARESGFSAEYFQH	11537
386	GGTFSSYA	11669	INPSGGST	11931	ARATGLYCSGSCFDY	11538
388	RSILDFNA	14122	IARAGAT	14123	NARVFDLPNDY	14124

LCDR1

LCDR2

LCDR3

265	QDISNY	13364	DAS		QQSYSTPLT	12714
266	QSISSY	13365	AAS		QQSYSTPLT	12715
267	QDISNY	13366	KAS		QQSFSSPLT	12716
263	QDISNY	13367	DAS		QQSYSTPLT	12717
268	QNVNTW	13368	EAS		QQANSFPFT	12718
269	QSISDW	13369	AAS		AQHNHYPYT	12719
272	QAIRDD	13370	DAS		QQANSFPIT	12722
273	QGVGND	13371	AAS		QQASSFPLT	12723
274	QIIGTN	13372	AAS		QQSYTFPVT	12724
275	QSISTW	13373	DAS		QQSYSTPFT	12725
281	QDIRNY	13374	DAS		QQAYSFPWT	12733
282	QDISNY	13375	NAS		QQLNSYPFT	12734
283	QSISTW	13376	AAS		LOHYTYPLT	12735
284	EDISTY	13377	AAS		QQSHTIPWT	12736
285	HHISDF	13378	AAS		QQSYSSPYT	12737
286	QDIGDY	13379	DAS		QQANSFPLT	12738
258	QDIGDY	13380	DAS		QQANSFPLT	12739
287	QDIRSY	13381	AAS		QQSYTAPPT	12740
288	QDISNN	13382	AAS		LOHNTYPLT	12741
289	QDISNW	13383	DAS		QQAISFPLT	12742
290	QGIANY	13384	AAS		QQADSFPLT	12743
291	QGIASY	13385	AAS		QQFDSYPIT	12744
260	QGIASY	13386	AAS		QQFDSYPIT	12745
292	QGISNY	13387	AAS		QQSSIIPFT	12746
293	QGISNY	13388	AAS		QQAYSFPYT	12747
294	QSIGRW	13389	DAS		QQSYSTPRT	12748
295	QSINSW	13390	DTS		QQTYSTPYT	12749
296	QSISSW	13391	AAS		QQGYSTPYI	12750
261	QSISSW	13392	AAS		QQGYSTPYI	12751
297	QSISSY	13393	AAS		QQTDSIPIT	12752
298	QSISSY	13394	AAS		QQSYSIPYT	12753
299	QTIRSY	13395	KAS		QQTYTIPIT	12754
300	QTISNW	13396	AAS		QQANSFPPT	12755
301	QYIGSY	13397	DAS		QQVDSYPLT	12756
307	QDIGNY	13398	AAS		QQTYNTPLT	12762
308	QDISNY	13399	EAS		QQSYSTPFT	12763
309	QDISTW	13400	RAS		QQSYSIPLT	12764
310	QNINNY	13401	AAS		QQSYSAPVT	12765
311	QNINTW	13402	AAS		QQAYSFPFT	12766
312	QRIGNY	13403	AAS		QQSYSTPLT	12767
313	QSISTY	13404	AAS		QQSYRTVT	12768
324	QDISNY	13405	AAS		QQSYSTPT	12779
325	QDISNY	13406	GAS		QEADSFPLT	12780
326	QGIRND	13407	DAS		QQAYSFPWT	12781
327	QGISNY	13408	KAS		QQSYNTPFT	12782
262	QGISNY	13409	KAS		QQSYNTPFT	12783
328	QSINRW	13410	SAS		QQSYNTPLT	12784
329	QSINTW	13411	AAS		QQANSFPFT	12785
330	QSIRTW	13412	DAS		QQLNSYPLT	12786
331	QSIRTY	13413	AAS		QQSYSAPLT	12787
332	QSISTY	13414	AAS		QQSYSTPLT	12788
333	QSITTY	13415	AAS		QQSYSTPLT	12789
339	QSISSW	13416	DAS		QQSYSTPFT	12795
340	QSISSY	13417	DAS		QQSYSFPT	12796
344	QDISNY	13418	AAA		QQTYSTPWT	12800
345	QDINTY	13419	AAS		QQSSSFPLT	12801
346	QDISNY	13420	AAS		QQLYNFPYT	12802
347	QSISRY	13421	GAS		QQSYNTPLT	12803
348	QTLSGW	13422	GAS		QQYYSYPPT	12804
349	QDIINY	13423	EAS		QQSYSTPLT	12805
350	QSISSY	13424	DVF		QQSYSSPFT	12806
351	QDISNY	13425	MAS		QQTNSFPLT	12807
352	QSISSY	13426	DAS		QQSYSTPLT	12808
356	ESVSTW	13427	KAS		QQSYKTPYT	12812
358	QSISSY	13428	AAS		QQSYSTPYT	12814
360	QSISSY	13429	KAS		QQNDSIPIT	12816
361	QSISRW	13430	DAS		LODYSYPLT	12817
363	QSINRY	13431	AAS		QQANSFPPT	12819
364	QGISNY	13432	SAS		QQSYSTPLT	12820
259	QGISNY	13433	SAS		QQSYSTPLT	12821
365	QSIDSY	13434	KAS		QQSYSAPLT	12822
366	QDISTW	13435	DAS		QQVNSDPYT	12823
367	QDISNY	13436	AAS		QQGDSLPLT	12824
368	QGISNY	13437	AAS		QQSDSFPYT	12825
370	QGIRND	13438	AAS		QQANSFPPT	12827
371	ESISTY	13439	KAS		QQTDSTFIT	12828
372	RNIHDY	13440	AAS		QQTYSTPPT	12829
373	QSNDSY	13441	KAS		QQSYSSPLT	12830
374	QSISDF	13442	AAS		QQSYSSPYT	12831
375	QDISNY	13443	AAS		QQANRFPLT	12832
376	QDISNY	13444	KAS		QQSYNFPAT	12833
378	QSISSY	13445	DAS		QQSYSTPLT	12835
379	QGISDY	13446	DAS		QQSYILPLT	12836
380	QDINDF	13447	AAS		QQSYSAPYT	12837
381	QSISNW	13448	AAS		QQSYSSPWT	12838
382	QGIDSW	13449	AAS		QQAYSFPLT	12839
383	QNIGTW	13450	RAS		QQAYSFPWT	12840
384	QNINNW	13451	KAS		QQADSFPPT	12841
385	QDISSY	13452	AAS		QQLNRYPIT	12842
386	QDISNY	13453	AAS		QQYDSSFIT	12843
302	QSLLHSNGYNY	13454	LGS		MQGTHWPPT	12757
303	QSLLHSNGYNY	13455	FGS		MQALQAPVS	12758
316	QSLLHSNGYNY	13456	DAS		MQALQTPPA	12771
334	QSLLHSNGYNY	13457	AAS		MQARQTPLT	12790
335	QSLLHSNGYNY	13458	GAS		MQTLQTPFT	12791
336	QSLLHSNGYNY	13459	LGS		MQALQTPLT	12792
353	QSLLHSNGYNY	13460	LGS		MQALQSPWT	12809
355	QSLLHSNGYNY	13461	LGS		MQALQTPPS	12811
377	QSLLHSNGYNY	13462	LGS		MQGTHWPET	12834
314	QSVGSY	13463	GAS		QQYDSSSQT	12769
315	RSVSTY	13464	GAS		QQYDGSPYT	12770
341	QSVSSY	13465	DTS		QQYYDTPYT	12797
369	QSVSTY	13466	GAS		QQHDSYPLT	12826
270	QSVLSSSYNKNY	13467	WAS		QQYYTTPFT	12720
271	QSVLSSSYNKNY	13468	WAS		QQYYSTPFT	12721
276	QSVLSSSNNKNY	13469	WAS		QQYYGSPLT	12726
277	QSVLSSSYNKNY	13470	WAS		QQYYSSPPT	12727
278	QSVLSSSYNKNY	13471	WAS		QQYYSSPPT	12728
279	QSVLSSSYNKNY	13472	WAS		QQYYSTPWT	12729
264	QSVLSSSYNKNY	13473	WAS		QQYYSTPWT	12730
257	QSVLSSSYNKNY	13474	WAS		QQYYSTPWT	12731
280	QSVLSSSYNKNY	13475	WAS		QQYYGSPPT	12732
304	QSVLSSSYNKNY	13476	WAS		QQYYSTPLT	12759
305	QSVSSSSYNKNY	13477	WAS		QQYYSTPIT	12760
306	QNVLSSSNNNSY	13478	WAS		QQYYSTPFT	12761
317	QSVLSSSYNKNF	13479	WAS		QQYYSAPPT	12772
318	QSVLSSSYNKNF	13480	WAS		QQYYSDPIT	12773
319	QSVLSSSYNKNY	13481	WAS		QQYYSIPIA	12774
320	QSVLSSSYNKNY	13482	WAS		QQYYSIPYT	12775
321	QSVLSTSYNKNY	13483	WAS		QQYYTTPPT	12776
322	QSVLSTSYNRNF	13484	WAS		QQYYSTPYT	12777
323	QSVLYSSNNKNY	13485	WAS		QQYYSTPLT	12778
337	QTVFSTSYNKNY	13486	WAS		QQYYSTPLT	12793
338	QSVFSTSYNRDY	13487	WAS		QQYYSSPPT	12794
342	QSVLYSSNNKNY	13488	LAS		QQYYSTPPT	12798
343	QSVLSSSYNKNY	13489	WAS		QQYYSTPLT	12799
354	QSVLYSSNNKNY	13490	WAS		QQYYSSPLT	12810
357	QSVLYSSNNKNY	13491	WAS		QQYFTTPLT	12813
359	QSVLSSSYNKNY	13492	WAS		QQYYDTPLT	12815
362	QSVFSTSYNRDY	13493	WAS		QQYYYTST	12818

TABLE 25
G and F Proteins

SEQ ID
NO:	SEQUENCE	ANNOTATION

9258	MVVILDKRCY CNLLILILMI SECSVGILHY	Nipah virus NiV-F
	EKLSKIGLVK GVTRKYKIKS NPLIKDIVIK	with signal sequence
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	(aa 1-546)
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI	Uniprot Q9IH63
	GIATAAQITA GVALYEAMKN ADNINKLKSS
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGF
	CLITKRSVIC NQDYATPMIN NMRECLTGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNTYSRLED RRVRPTSSGD LYYIGT
9259	ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK	Nipah virus NiV-F F0
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	(aa 27-546)
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI
	GIATAAQITA GVALYEAMKN ADNINKLKSS
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDEDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGF
	CLITKRSVIC NQDYATPMIN NMRECLTGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNTYSRLED RRVRPTSSGD LYYIGT
9260	ILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIKMIPNVS	Nipah virus NiV-F F2
	NMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVG	(aa 27-109)
	DVR
9261	LAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKS	Nipah virus NiV F F1
	SIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDK	(aa 110-546)
	ISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQ
	AISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYV
	DLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWI
	SIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMT
	NNMRECLIGSTEKCPRELVVSSHVPRFALSNGVLFANCIS
	VTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISL
	GKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQ
	SKDYIKEAQRLLDTVNPSLISMLSMIILYVLSIASLCIGL
	ITFISFIIVEKKRNTYSRLEDRRVRPTSSGDLYYIGT
9262	ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK	Nipah virus NiV-F F0
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	(aa T234 truncation
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI	525-544)
	GIATAAQITA GVALYEAMKN ADNINKLKSS
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGE
	CLITKRSVIC NQDYATPMIN NMRECLTGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNTGT
9263	LAGVIMAGVAIGIATAAQITAGVALYEAMKNADNINKLKS	Nipah virus NiV F F1
	SIESTNEAVVKLQETAEKTVYVLTALQDYINTNLVPTIDK	(aa 110-546)
	ISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQ	truncation
	AISQAFGGNYETLLRTLGYATEDFDDLLESDSITGQIIYV	(aa 525-544)
	DLSSYYIIVRVYFPILTEIQQAYIQELLPVSFNNDNSEWI
	SIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMT
	NNMRECLTGSTEKCPRELVVSSHVPRFALSNGVLFANCIS
	VTCQCQTTGRAISQSGEQTLLMIDNTTCPTAVLGNVIISL
	GKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQ
	SKDYIKEAQRLLDTVNPSLISMLSMIILYVLSIASLCIGL
	ITFISFIIVEKKRNTGT
9264	ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK	Nipah virus NiV-F F0
	MIPNVSNMSQ CTGSVMENYK TRINGILIPI	T234 truncation (aa
	KGALEIYKNQ THDLVGDVRL AGVIMAGVAI	525-544) AND
	GIATAAQITA GVALYEAMKN ADNINKLKSS	mutation on N-linked
	IESTNEAVVK LQETAEKTVY VLTALQDYIN	glycosylation site
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGE
	CLITKRSVIC NQDYATPMIN NMRECLIGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNTGT
9265	MVVILDKRCY CNLLILILMI SECSVGILHY	Truncated NiV fusion
	EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK	glycoprotein
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	(FcDelta22) at
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI	cytoplasmic tail
	GIATAAQITA GVALYEAMKN ADNINKLKSS	(with signal sequence)
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGF
	CLITKRSVIC NQDYATPMTN NMRECLTGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNT
9266	MGPAENKKVR FENTTSDKGK IPSKVIKSYY	NiVG protein
	GTMDIKKINE GLLDSKILSA FNTVIALLGS	attachment
	IVIIVMNIMI IQNYTRSTDN QAVIKDALQG	glycoprotein (602 aa)
	IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT
	IPANIGLLGS KISQSTASIN ENVNEKCKFT
	LPPLKIHECN ISCPNPLPFR EYRPQTEGVS
	NLVGLPNNIC LQKTSNQILK PKLISYTLPV
	VGQSGTCITD PLLAMDEGYF AYSHLERIGS
	CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN
	VWTPPNPNTV YHCSAVYNNE FYYVLCAVST
	VGDPILNSTY WSGSLMMTRL AVKPKSNGGG
	YNQHQLALRS IEKGRYDKVM PYGPSGIKQG
	DTLYFPAVGF LVRTEFKYND SNCPITKCQY
	SKPENCRLSM GIRPNSHYIL RSGLLKYNLS
	DGENPKVVFI EISDQRLSIG SPSKIYDSLG
	QPVFYQASFS WDTMIKFGDV LTVNPLVVNW
	RNNTVISRPG QSQCPRENTC PEICWEGVYN
	DAFLIDRINW ISAGVFLDSN QTAENPVFTV
	FKDNEILYRA QLASEDTNAQ KTITNCFLLK
	NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC
9267	MGKVR FENTTSDKGK IPSKVIKSYY GTMDIKKINE	NiVG protein
	GLLDSKILSA FNTVIALLGS IVIIVMNIMI	attachment
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	glycoprotein
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	Truncated Δ5
	KISQSTASIN ENVNEKCKFT LPPLKIHECN
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC
	LQKTSNQILK PKLISYTLPV VGQSGTCITD
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI
	IGVGEVLDRG DEVPSLFMIN VWTPPNPNTV
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PEICWEGVYN DAFLIDRINW

	ISAGVFLDSN QTAENPVFTV FKDNEILYRA
	QLASEDINAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QC
9268	MGNTTSDKGK IPSKVIKSYY GTMDIKKINE	NiVG protein
	GLLDSKILSA FNTVIALLGS IVIIVMNIMI	attachment
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	glycoprotein
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	Truncated Δ10
	KISQSTASIN ENVNEKCKFT LPPLKIHECN
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC
	LQKTSNQILK PKLISYTLPV VGQSGTCITD
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI
	IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PEICWEGVYN DAFLIDRINW
	ISAGVFLDSN QTAENPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QC
9269	MGKGK IPSKVIKSYY GIMDIKKINE GLLDSKILSA	NiVG protein
	FNTVIALLGS IVIIVMNIMI IQNYTRSTDN	attachment
	QAVIKDALQG IQQQIKGLAD KIGTEIGPKV	glycoprotein
	SLIDTSSTIT IPANIGLLGS KISQSTASIN	Truncated Δ15
	ENVNEKCKFT LPPLKIHECN ISCPNPLPER
	EYRPQTEGVS NLVGLPNNIC LQKTSNQILK
	PKLISYTLPV VGQSGICITD PLLAMDEGYF
	AYSHLERIGS CSRGVSKQRI IGVGEVLDRG
	DEVPSLFMIN VWTPPNPNTV YHCSAVYNNE
	FYYVLCAVST VGDPILNSTY WSGSLMMTRL
	AVKPKSNGGG YNQHQLALRS IEKGRYDKVM
	PYGPSGIKQG DTLYFPAVGF LVRIEFKYND
	SNCPITKCQY SKPENCRLSM GIRPNSHYIL
	RSGLLKYNLS DGENPKVVFI EISDQRLSIG
	SPSKIYDSLG QPVFYQASFS WDTMIKFGDV
	LTVNPLVVNW RNNTVISRPG QSQCPRENTC
	PEICWEGVYN DAFLIDRINW ISAGVFLDSN
	QTAENPVFTV FKDNEILYRA QLASEDTNAQ
	KTITNCFLLK NKIWCISLVE IYDTGDNVIR
	PKLFAVKIPE QC

9270	MGSKVIKSYY GTMDIKKINE GLLDSKILSA	NiVG protein
	FNTVIALLGS IVIIVMNIMI IQNYTRSTDN	attachment
	QAVIKDALQG IQQQIKGLAD KIGTEIGPKV	glycoprotein
	SLIDTSSTIT IPANIGLLGS KISQSTASIN	Truncated Δ20
	ENVNEKCKFT LPPLKIHECN ISCPNPLPER
	EYRPQTEGVS NLVGLPNNIC LQKTSNQILK
	PKLISYTLPV VGQSGTCITD PLLAMDEGYF
	AYSHLERIGS CSRGVSKQRI IGVGEVLDRG
	DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE
	FYYVLCAVST VGDPILNSTY WSGSLMMTRL
	AVKPKSNGGG YNQHQLALRS IEKGRYDKVM
	PYGPSGIKQG DTLYFPAVGF LVRIEFKYND
	SNCPITKCQY SKPENCRLSM GIRPNSHYIL
	RSGLLKYNLS DGENPKVVFI EISDQRLSIG
	SPSKIYDSLG QPVFYQASFS WDTMIKFGDV
	LTVNPLVVNW RNNTVISRPG QSQCPRENTC
	PEICWEGVYN DAFLIDRINW ISAGVELDSN
	QTAENPVFTV FKDNEILYRA QLASEDTNAQ
	KTITNCFLLK NKIWCISLVE IYDTGDNVIR
	PKLFAVKIPE QC
9271	MGSYY GTMDIKKINE GLLDSKILSA FNTVIALLGS	NiVG protein
	IVIIVMNIMI IQNYTRSTDN QAVIKDALQG	attachment
	IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT	glycoprotein
	IPANIGLLGS KISQSTASIN ENVNEKCKFT	Truncated Δ25
	LPPLKIHECN ISCPNPLPER EYRPQTEGVS
	NLVGLPNNIC LQKTSNQILK PKLISYTLPV
	VGQSGTCITD PLLAMDEGYF AYSHLERIGS
	CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN
	VWTPPNPNTV YHCSAVYNNE FYYVLCAVST
	VGDPILNSTY WSGSLMMTRL AVKPKSNGGG
	YNQHQLALRS IEKGRYDKVM PYGPSGIKQG
	DTLYFPAVGF LVRTEFKYND SNCPITKCQY
	SKPENCRLSM GIRPNSHYIL RSGLLKYNLS
	DGENPKVVFI EISDQRLSIG SPSKIYDSLG
	QPVFYQASFS WDTMIKFGDV LTVNPLVVNW
	RNNTVISRPG QSQCPRENTC PEICWEGVYN
	DAFLIDRINW ISAGVFLDSN QTAENPVFTV
	FKDNEILYRA QLASEDTNAQ KTITNCFLLK
	NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC
9272	MGTMDIKKINE GLLDSKILSA FNTVIALLGS	NiVG protein
	IVIIVMNIMI IQNYTRSTDN QAVIKDALQG	attachment
	IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT	glycoprotein
	IPANIGLLGS KISQSTASIN ENVNEKCKFT	Truncated Δ30
	LPPLKIHECN ISCPNPLPER EYRPQTEGVS
	NLVGLPNNIC LQKTSNQILK PKLISYTLPV
	VGQSGTCITD PLLAMDEGYF AYSHLERIGS
	CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN
	VWTPPNPNTV YHCSAVYNNE FYYVLCAVST
	VGDPILNSTY WSGSLMMTRL AVKPKSNGGG
	YNQHQLALRS IEKGRYDKVM PYGPSGIKQG
	DTLYFPAVGF LVRTEFKYND SNCPITKCQY
	SKPENCRLSM GIRPNSHYIL RSGLLKYNLS
	DGENPKVVFI EISDQRLSIG SPSKIYDSLG
	QPVFYQASFS WDTMIKFGDV LTVNPLVVNW
	RNNTVISRPG QSQCPRENTC PEICWEGVYN
	DAFLIDRINW ISAGVELDSN QTAENPVFTV
	FKDNEILYRA QLASEDTNAQ KTITNCFLLK
	NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC
9273	MKKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI	NiVG protein
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	attachment
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	glycoprotein
	KISQSTASIN ENVNEKCKFT LPPLKIHECN	Truncated and
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC	mutated
	LQKTSNQILK PKLISYTLPV VGQSGTCITD	(E501A, W504A,
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI	Q530A, E533A) NIV G
	IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV	protein (Gc Δ 34)
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PAICAEGVYN DAFLIDRINW
	ISAGVFLDSN ATAANPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QCT
9274	MATQEVRLKC LLCGIIVLVL SLEGLGILHY	Hendra virus F protein
	EKLSKIGLVK GITRKYKIKS	Uniprot O89342 (with
	NPLTKDIVIK MIPNVSNVSK CTGTVMENYK	signal sequence)
	SRLIGILSPI KGAIELYNNN
	THDLVGDVKL AGVVMAGIAI GIATAAQITA
	GVALYEAMKN ADNINKLKSS
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDQI SCKQTELALD
	LALSKYLSDL LFVFGPNLQD PVSNSMTIQA
	ISQAFGGNYE TLLRTLGYAT EDFDDLLESD
	SIAGQIVYVD LSSYYIIVRV YFPILTEIQQ
	AYVQELLPVS
	FNNDNSEWIS IVPNFVLIRN TLISNIEVKY
	CLITKKSVIC NQDYATPMTA
	SVRECLIGST DKCPRELVVS SHVPRFALSG
	GVLFANCISV TCQCQTTGRA ISQSGEQTLL
	MIDNTTCTTV VLGNIIISLG KYLGSINYNS
	ESIAVGPPVY
	TDKVDISSQI SSMNQSLQQS KDYIKEAQKI
	LDTVNPSLIS MLSMIILYVL
	SIAALCIGLI TFISFVIVEK KRGNYSRLDD
	RQVRPVSNGD LYYIGT
9275	MMADSKLVSL NNNLSGKIKD QGKVIKNYYG	Hendra virus G protein
	TMDIKKINDG LLDSKILGAF	Uniprot O89343
	NTVIALLGSI IIIVMNIMII QNYTRTTDNQ
	ALIKESLQSV QQQIKALTDK IGTEIGPKVS
	LIDTSSTITI PANIGLLGSK ISQSTSSINE
	NVNDKCKFTL
	PPLKIHECNI SCPNPLPFRE YRPISQGVSD
	LVGLPNQICL QKTTSTILKP RLISYTLPIN
	TREGVCITDP LLAVDNGFFA YSHLEKIGSC
	TRGIAKQRII GVGEVLDRGD KVPSMFMTNV
	WTPPNPSTIH HCSSTYHEDF YYTLCAVSHV
	GDPILNSTSW TESLSLIRLA VRPKSDSGDY
	NQKYIAITKV ERGKYDKVMP
	YGPSGIKQGD TLYFPAVGFL PRTEFQYNDS
	NCPIIHCKYS KAENCRLSMG
	VNSKSHYILR SGLLKYNLSL GGDIILQFIE
	IADNRLTIGS PSKIYNSLGQ PVFYQASYSW
	DTMIKLGDVD TVDPLRVQWR NNSVISRPGQ
	SQCPRFNVCP
	EVCWEGTYND AFLIDRLNWV SAGVYLNSNQ
	TAENPVFAVF KDNEILYQVP LAEDDTNAQK
	TITDCFLLEN VIWCISLVEI YDTGDSVIRP
	KLFAVKIPAQ CSES
9276	MVVILDKRCY CNLLILILMI SECSVGILHY	Nipah virus NiV-F FO
	EKLSKIGLVK GVTRKYKIKS NPLIKDIVIK	T234 truncation (aa
	MIPNVSNMSQ CTGSVMENYK TRINGILTPI	525-544) (with signal
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI	sequence)
	GIATAAQITA GVALYEAMKN ADNINKLKSS
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGE
	CLITKRSVIC NQDYATPMIN NMRECLTGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNTGT
9277	MVVILDKRCY CNLLILILMI SECSVGILHY	Nipah virus NiV-F F0
	EKLSKIGLVK GVTRKYKIKS NPLIKDIVIK	T234 truncation (aa
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	525-544) AND
	KGALEIYKNQ THDLVGDVRL AGVIMAGVAI	mutation on N-linked
	GIATAAQITA GVALYEAMKN ADNINKLKSS	glycosylation site
	IESTNEAVVK LQETAEKTVY VLTALQDYIN	(with signal sequence)
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGF
	CLITKRSVIC NQDYATPMIN NMRECLTGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNTGT
9278	MVVILDKRCY CNLLILILMI SECSVGILHY	Truncated NiV fusion
	EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK	glycoprotein
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	(FcDelta22) at
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI	cytoplasmic tail (with
	GIATAAQITA GVALYEAMKN ADNINKLKSS	signal sequence)
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGE
	CLITKRSVIC NQDYATPMIN NMRECLIGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVE
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNT
9279	MKKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI	NiVG protein
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	attachment
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	glycoprotein
	KISQSTASIN ENVNEKCKFT LPPLKIHECN	Truncated (Gc Δ 34)
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC
	LQKTSNQILK PKLISYTLPV VGQSGTCITD
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI
	IGVGEVLDRG DEVPSLFMIN VWTPPNPNTV
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PEICWEGVYN DAFLIDRINW
	ISAGVFLDSN QTAENPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QCT
9280	ILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK	Truncated mature NiV
	MIPNVSNMSQ CTGSVMENYK TRLNGILTPI	fusion glycoprotein
	KGALEIYKNN THDLVGDVRL AGVIMAGVAI	(FcDelta22) at
	GIATAAQITA GVALYEAMKN ADNINKLKSS	cytoplasmic tail
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDKI SCKQTELSLD LALSKYLSDL
	LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE
	TLLRTLGYAT EDFDDLLESD SITGQIIYVD
	LSSYYIIVRV YFPILTEIQQ AYIQELLPVS
	FNNDNSEWIS IVPNFILVRN TLISNIEIGF
	CLITKRSVIC NQDYATPMIN NMRECLIGST
	EKCPRELVVS SHVPRFALSN GVLFANCISV
	TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA
	VLGNVIISLG KYLGSVNYNS EGIAIGPPVF
	TDKVDISSQI SSMNQSLQQS KDYIKEAQRL
	LDTVNPSLIS MLSMIILYVL SIASLCIGLI
	TFISFIIVEK KRNT
9281	MSNKRITVLIIISYTLFYLNNAAIVGFDFDKLNKIGVVQG	gb: JQ001776:6129-
	RVLNYKIKGDPMTKDLVLKFIPNIVNITECVREPLSRYNE	8166|Organism: Cedar
	TVRRLLLPIHNMLGLYLNNTNAKMTGLMIAGVIMGGIAIG	virus|Strain
	IATAAQITAGFALYEAKKNTENIQKLIDSIMKTQDSIDKL	Name: CG1a|Protein
	TDSVGTSILILNKLQTYINNQLVPNLELLSCRQNKIEFDL	Name: fusion
	MLTKYLVDLMTVIGPNINNPVNKDMTIQSLSLLFDGNYDI	glycoprotein|Gene
	MMSELGYTPQDFLDLIESKSITGQIIYVDMENLYVVIRTY	Symbol: F (with signal
	LPTLIEVPDAQIYEFNKITMSSNGGEYLSTIPNFILIRGN	sequence)
	YMSNIDVATCYMTKASVICNQDYSLPMSQNLRSCYQGETE
	YCPVEAVIASHSPRFALINGVIFANCINTICRCQDNGKTI
	TQNINQFVSMIDNSTCNDVMVDKFTIKVGKYMGRKDINNI
	NIQIGPQIIIDKVDLSNEINKMNQSLKDSIFYLREAKRIL
	DSVNISLISPSVQLFLIIISVLSFIILLIIIVYLYCKSKH
	SYKYNKFIDDPDYYNDYKRERINGKASKSNNIYYVGD
9282	MALNKNMFSSLFLGYLLVYATTVQSSIHYDSLSKVGVIKG	gb: NC_025352:5950-
	LTYNYKIKGSPSTKLMVVKLIPNIDSVKNCTQKQYDEYKN	8712|Organism: Mojiang
	LVRKALEPVKMAIDTMLNNVKSGNNKYRFAGAIMAGVALG	virus|Strain
	VATAATVTAGIALHRSNENAQAIANMKSAIQNTNEAVKQL	Name: Tongguan1|Protein
	QLANKQTLAVIDTIRGEINNNIIPVINQLSCDTIGLSVGI	Name: fusion
	RLTQYYSEIITAFGPALQNPVNTRITIQAISSVENGNFDE	protein|Gene
	LLKIMGYTSGDLYEILHSELIRGNIIDVDVDAGYIALEIE	Symbol: F (with signal
	FPNLTLVPNAVVQELMPISYNIDGDEWVTLVPRFVLTRIT	sequence)
	LLSNIDTSRCTITDSSVICDNDYALPMSHELIGCLQGDTS
	KCAREKVVSSYVPKFALSDGLVYANCLNTICRCMDTDTPI
	SQSLGATVSLLDNKRCSVYQVGDVLISVGSYLGDGEYNAD
	NVELGPPIVIDKIDIGNQLAGINQTLQEAEDYIEKSEEFL
	KGVNPSIITLGSMVVLYIFMILIAIVSVIALVLSIKLTVK
	GNVVRQQFTYTQHVPSMENINYVSH
9283	MKKKTDNPTISKRGHNHSRGIKSRALLRETDNYSNGLIVE	gb: NC_025256:6865-
	NLVRNCHHPSKNNLNYTKTQKRDSTIPYRVEERKGHYPKI	8853|Organism: Bat
	KHLIDKSYKHIKRGKRRNGHNGNIITIILLLILILKTQMS	Paramyxovirus
	EGAIHYETLSKIGLIKGITREYKVKGTPSSKDIVIKLIPN	Eid_hel/GH-
	VTGLNKCTNISMENYKEQLDKILIPINNIIELYANSTKSA	M74a/GHA/2009|Strain
	PGNARFAGVIIAGVALGVAAAAQITAGIALHEARQNAERI	Name: BatPV/Eid_hel/
	NLLKDSISATNNAVAELQEATGGIVNVITGMQDYININLV	GH-M74a/GHA/2009|
	PQIDKLQCSQIKTALDISLSQYYSEILTVFGPNLQNPVTT	Protein
	SMSIQAISQSFGGNIDLLLNLLGYTANDLLDLLESKSITG	Name: fusion
	QITYINLEHYFMVIRVYYPIMTTISNAYVQELIKISFNVD	protein|Gene
	GSEWVSLVPSYILIRNSYLSNIDISECLITKNSVICRHDF	Symbol: F (with signal
	AMPMSYTLKECLTGDTEKCPREAVVTSYVPRFAISGGVIY	sequence)
	ANCLSTTCQCYQTGKVIAQDGSQTLMMIDNQTCSIVRIEE
	ILISTGKYLGSQEYNTMHVSVGNPVFTDKLDITSQISNIN
	QSIEQSKFYLDKSKAILDKINLNLIGSVPISILFIIAILS
	LILSIITFVIVMIIVRRYNKYTPLINSDPSSRRSTIQDVY
	IIPNPGEHSIRSAARSIDRDRD
9284	(GGGGGS)n wherein n is 1 to 6	Peptide Linker
9285	MPAENKKVRFENTTSDKGKIPSKVIKSYYGTMDIKKINEG	gb: AF212302|Organism:
	LLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQ	Nipah virus|Strain
	AVIKDALQGIQQQIKGLADKIGTEIGPKVSLIDTSSTITI	Name: UNKNOWN-
	PANIGLLGSKISQSTASINENVNEKCKFTLPPLKIHECNI	AF212302|Protein
	SCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKP	Name: attachment
	KLISYTLPVVGQSGTCITDPLLAMDEGYFAYSHLERIGSC	glycoprotein|Gene
	SRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTPPNPNTVY	Symbol: G
	HCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLA	(Uniprot Q9IH62)
	VKPKSNGGGYNQHQLALRSIEKGRYDKVMPYGPSGIKQGD
	TLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPENCRLSMG
	IRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGS
	PSKIYDSLGQPVFYQASFSWDTMIKFGDVLTVNPLVVNWR
	NNTVISRPGQSQCPRFNTCPEICWEGVYNDAFLIDRINWI
	SAGVFLDSNQTAENPVFTVFKDNEILYRAQLASEDTNAQK
	TITNCFLLKNKIWCISLVEIYDTGDNVIRPKLFAVKIPEQ
	CT
9286	MLSQLQKNYLDNSNQQGDKMNNPDKKLSVNFNPLELDKGQ	gb: JQ001776:8170-
	KDLNKSYYVKNKNYNVSNLLNESLHDIKFCIYCIFSLLII	10275|Organism: Cedar
	ITIINIITISIVITRLKVHEENNGMESPNLQSIQDSLSSL	virus|Strain
	TNMINTEITPRIGILVTATSVTLSSSINYVGTKTNQLVNE	Name: CG1a|Protein
	LKDYITKSCGFKVPELKLHECNISCADPKISKSAMYSTNA	Name: attachment
	YAELAGPPKIFCKSVSKDPDFRLKQIDYVIPVQQDRSICM	glycoprotein|Gene
	NNPLLDISDGFFTYIHYEGINSCKKSDSFKVLLSHGEIVD	Symbol: G
	RGDYRPSLYLLSSHYHPYSMQVINCVPVTCNQSSFVFCHI
	SNNTKTLDNSDYSSDEYYITYFNGIDRPKTKKIPINNMTA
	DNRYIHFTFSGGGGVCLGEEFIIPVTTVINTDVFTHDYCE
	SFNCSVQTGKSLKEICSESLRSPINSSRYNLNGIMIISQN
	NMTDFKIQLNGITYNKLSFGSPGRLSKTLGQVLYYQSSMS
	WDTYLKAGFVEKWKPFTPNWMNNTVISRPNQGNCPRYHKC
	PEICYGGTYNDIAPLDLGKDMYVSVILDSDQLAENPEITV
	FNSTTILYKERVSKDELNTRSTTTSCFLFLDEPWCISVLE
	TNRFNGKSIRPEIYSYKIPKYC
9287	MPQKTVEFINMNSPLERGVSTLSDKKTLNQSKITKQGYFG	gb: NC_025256:9117-
	LGSHSERNWKKQKNQNDHYMTVSIMILEILVVLGIMENLI	11015|Organism: Bat
	VLTMVYYQNDNINQRMAELTSNITVLNLNLNQLINKIQRE	Paramyxovirus
	IIPRITLIDTATTITIPSAITYILATLITRISELLPSINQ	Eid_hel/GH-
	KCEFKTPTLVLNDCRINCTPPLNPSDGVKMSSLATNLVAH	M74a/GHA/2009|Strain
	GPSPCRNFSSVPTIYYYRIPGLYNRTALDERCILNPRLTI	Name: BatPV/Eid_hel/
	SSTKFAYVHSEYDKNCTRGFKYYELMTFGEILEGPEKEPR	GH-
	MFSRSFYSPTNAVNYHSCTPIVTVNEGYFLCLECTSSDPL	M74a/GHA/2009|Protein
	YKANLSNSTFHLVILRHNKDEKIVSMPSFNLSTDQEYVQI	Name: glycoprotein|
	IPAEGGGTAESGNLYFPCIGRLLHKRVTHPLCKKSNCSRT	Gene Symbol: G
	DDESCLKSYYNQGSPQHQVVNCLIRIRNAQRDNPTWDVIT
	VDLTNTYPGSRSRIFGSFSKPMLYQSSVSWHTLLQVAEIT
	DLDKYQLDWLDTPYISRPGGSECPFGNYCPTVCWEGTYND
	VYSLTPNNDLFVTVYLKSEQVAENPYFAIFSRDQILKEFP
	LDAWISSARTTTISCFMFNNEIWCIAALEITRLNDDIIRP
	IYYSFWLPTDCRTPYPHTGKMTRVPLRSTYNY
9288	MATNRDNTITSAEVSQEDKVKKYYGVETAEKVADSISGNK	gb: NC_025352:8716-
	VFILMNTLLILTGAIITITLNITNLTAAKSQQNMLKIIQD	11257|Organism: Mojiang
	DVNAKLEMFVNLDQLVKGEIKPKVSLINTAVSVSIPGQIS	virus|Strain
	NLQTKFLQKYVYLEESITKQCTCNPLSGIFPTSGPTYPPT	Name: Tongguan1|
	DKPDDDTTDDDKVDTTIKPIEYPKPDGCNRTGDHFTMEPG	Protein Name:
	ANFYTVPNLGPASSNSDECYTNPSFSIGSSIYMFSQEIRK	attachment
	TDCTAGEILSIQIVLGRIVDKGQQGPQASPLLVWAVPNPK	glycoprotein|Gene
	IINSCAVAAGDEMGWVLCSVTLTAASGEPIPHMEDGEWLY	Symbol: G
	KLEPDTEVVSYRITGYAYLLDKQYDSVFIGKGGGIQKGND
	LYFQMYGLSRNRQSFKALCEHGSCLGTGGGGYQVLCDRAV
	MSFGSEESLITNAYLKVNDLASGKPVIIGQTFPPSDSYKG
	SNGRMYTIGDKYGLYLAPSSWNRYLRFGITPDISVRSTTW
	LKSQDPIMKILSTCTNTDRDMCPEICNTRGYQDIFPLSED
	SEYYTYIGITPNNGGTKNFVAVRDSDGHIASIDILQNYYS
	ITSATISCFMYKDEIWCIAITEGKKQKDNPQRIYAHSYKI
	RQMCYNMKSATVTVGNAKNITIRRY
9289	FNTVIALLGS IVIIVMNIMI IQNYTRSTDN	NivG protein
	QAVIKDALQG IQQQIKGLAD KIGTEIGPKV	attachment
	SLIDTSSTIT IPANIGLLGS KISQSTASIN	glycoprotein
	ENVNEKCKFT LPPLKIHECN ISCPNPLPER	Without cytoplasmic
	EYRPQTEGVS NLVGLPNNIC LQKTSNQILK	tail
	PKLISYTLPV VGQSGTCITD PLLAMDEGYF	Uniprot Q9IH62
	AYSHLERIGS CSRGVSKQRI IGVGEVLDRG
	DEVPSLFMIN VWTPPNPNTV YHCSAVYNNE
	FYYVLCAVST VGDPILNSTY WSGSLMMTRL
	AVKPKSNGGG YNQHQLALRS IEKGRYDKVM
	PYGPSGIKQG DTLYFPAVGF LVRTEFKYND
	SNCPITKCQY SKPENCRLSM GIRPNSHYIL
	RSGLLKYNLS DGENPKVVFI EISDQRLSIG
	SPSKIYDSLG QPVFYQASFS WDTMIKFGDV
	LTVNPLVVNW RNNTVISRPG
	PEICWEGVYN DAFLIDRINW ISAGVELDSN
	QTAENPVFTV FKDNEILYRA QLASEDTNAQ
	KTITNCFLLK NKIWCISLVE IYDIGDNVIR
	PKLFAVKIPE QC
9290	FNTVIALLGSI IIIVMNIMII QNYTRTTDNQ	Hendra virus G protein
	ALIKESLQSV QQQIKALTDK	Uniprot O89343
	IGTEIGPKVS LIDTSSTITI PANIGLLGSK	Without cytoplasmic
	ISQSTSSINE NVNDKCKFTL	tail
	PPLKIHECNI SCPNPLPFRE	YRPISQGVSD
	LVGLPNQICL QKITSTILKP
	RLISYTLPIN TREGVCITDP LLAVDNGFFA
	YSHLEKIGSC TRGIAKQRII
	GVGEVLDRGD KVPSMFMTNV WTPPNPSTIH
	HCSSTYHEDF YYTLCAVSHV
	GDPILNSTSW TESLSLIRLA VRPKSDSGDY
	NQKYIAITKV ERGKYDKVMP
	YGPSGIKQGD TLYFPAVGFL PRTEFQYNDS
	NCPIIHCKYS KAENCRLSMG
	VNSKSHYILR SGLLKYNLSL GGDIILQFIE
	IADNRLTIGS PSKIYNSLGQ
	PVFYQASYSW DTMIKLGDVD TVDPLRVQWR
	NNSVISRPGQ SQCPRFNVCP EVCWEGTYND
	AFLIDRLNWV SAGVYLNSNQ TAENPVFAVF
	KDNEILYQVP LAEDDTNAQK TITDCFLLEN
	VIWCISLVEI YDIGDSVIRP KLFAVKIPAQ CSES
9291	MVVILDKRCY CNLLILILMI SECSVG	Signal sequence
9292	GGGGGS	Peptide linker
9293	(GGGGS)n wherein n is 1 to 10	Peptide linker
9294	GGGGS	Peptide linker
9295	PAENKKVR FENTTSDKGK IPSKVIKSYY	NiVG protein
	GTMDIKKINE GLLDSKILSA FNTVIALLGS	attachment
	IVIIVMNIMI IQNYTRSTDN QAVIKDALQG	glycoprotein (602 aa)
	IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT	Without N-terminal
	IPANIGLLGS KISQSTASIN ENVNEKCKFT	methionine
	LPPLKIHECN ISCPNPLPFR EYRPQTEGVS
	NLVGLPNNIC LQKTSNQILK PKLISYTLPV
	VGQSGTCITD PLLAMDEGYF AYSHLERIGS
	CSRGVSKQRI IGVGEVLDRG DEVPSLFMIN
	VWTPPNPNTV YHCSAVYNNE FYYVLCAVST
	VGDPILNSTY WSGSLMMTRL AVKPKSNGGG
	YNQHQLALRS IEKGRYDKVM PYGPSGIKQG
	DTLYFPAVGF LVRTEFKYND SNCPITKCQY
	SKPENCRLSM GIRPNSHYIL RSGLLKYNLS
	DGENPKVVFI EISDQRLSIG SPSKIYDSLG
	QPVFYQASFS WDTMIKFGDV LTVNPLVVNW
	RNNTVISRPG QSQCPRENTC PEICWEGVYN
	DAFLIDRINW ISAGVELDSN QTAENPVFTV
	FKDNEILYRA QLASEDTNAQ KTITNCFLLK
	NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC
9296	KVR FENTTSDKGK IPSKVIKSYY GTMDIKKINE	NiVG protein
	GLLDSKILSA FNTVIALLGS IVIIVMNIMI	attachment
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	glycoprotein
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	Truncated Δ5 Without
	KISQSTASIN ENVNEKCKFT LPPLKIHECN	N-terminal methionine
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC
	LQKTSNQILK PKLISYTLPV VGQSGTCITD
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI
	IGVGEVLDRG DEVPSLFMIN VWTPPNPNTV
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PEICWEGVYN DAFLIDRINW
	ISAGVFLDSN QTAENPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QC
9297	NTTSDKGK IPSKVIKSYY GTMDIKKINE	NiVG protein
	GLLDSKILSA FNTVIALLGS IVIIVMNIMI	attachment
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	glycoprotein
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	Truncated Δ10
	KISQSTASIN ENVNEKCKFT LPPLKIHECN	Without N-terminal
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC	methionine
	LQKTSNQILK PKLISYTLPV VGQSGTCITD
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI
	IGVGEVLDRG DEVPSLFMIN VWTPPNPNTV
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PEICWEGVYN DAFLIDRINW
	ISAGVFLDSN QTAENPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QC
9298	KGK IPSKVIKSYY GTMDIKKINE GLLDSKILSA	NiVG protein
	FNTVIALLGS IVIIVMNIMI IQNYTRSTDN	attachment
	QAVIKDALQG IQQQIKGLAD KIGTEIGPKV	glycoprotein
	SLIDTSSTIT IPANIGLLGS KISQSTASIN	Truncated Δ15
	ENVNEKCKFT LPPLKIHECN ISCPNPLPER	Without N-terminal
	EYRPQTEGVS NLVGLPNNIC LQKTSNQILK	methionine
	PKLISYTLPV VGQSGTCITD PLLAMDEGYF
	AYSHLERIGS CSRGVSKQRI IGVGEVLDRG
	DEVPSLFMIN VWTPPNPNTV YHCSAVYNNE
	FYYVLCAVST VGDPILNSTY WSGSLMMTRL
	AVKPKSNGGG YNQHQLALRS IEKGRYDKVM
	PYGPSGIKQG DTLYFPAVGF LVRTEFKYND
	SNCPITKCQY SKPENCRLSM GIRPNSHYIL
	RSGLLKYNLS DGENPKVVFI EISDQRLSIG
	SPSKIYDSLG QPVFYQASFS WDTMIKFGDV
	LTVNPLVVNW RNNTVISRPG QSQCPRENTC
	PEICWEGVYN DAFLIDRINW ISAGVELDSN
	QTAENPVFTV FKDNEILYRA QLASEDINAQ
	KTITNCFLLK NKIWCISLVE IYDTGDNVIR
	PKLFAVKIPE QC
9299	SKVIKSYY GTMDIKKINE GLLDSKILSA	NiVG protein
	FNTVIALLGS IVIIVMNIMI IQNYTRSTDN	attachment
	QAVIKDALQG IQQQIKGLAD KIGTEIGPKV	glycoprotein
	SLIDTSSTIT IPANIGLLGS KISQSTASIN	Truncated Δ20
	ENVNEKCKFT LPPLKIHECN ISCPNPLPER	Without N-terminal
	EYRPQTEGVS NLVGLPNNIC LQKTSNQILK	methionine
	PKLISYTLPV VGQSGTCITD PLLAMDEGYF
	AYSHLERIGS CSRGVSKQRI IGVGEVLDRG
	DEVPSLFMTN VWTPPNPNTV YHCSAVYNNE
	FYYVLCAVST VGDPILNSTY WSGSLMMTRL
	AVKPKSNGGG YNQHQLALRS IEKGRYDKVM
	PYGPSGIKQG DTLYFPAVGF LVRTEFKYND
	SNCPITKCQY SKPENCRLSM GIRPNSHYIL
	RSGLLKYNLS DGENPKVVFI EISDQRLSIG
	SPSKIYDSLG QPVFYQASFS WDTMIKFGDV
	LTVNPLVVNW RNNTVISRPG QSQCPRFNTC
	PEICWEGVYN DAFLIDRINW ISAGVFLDSN
	QTAENPVFTV FKDNEILYRA QLASEDINAQ
	KTITNCFLLK NKIWCISLVE IYDTGDNVIR
	PKLFAVKIPE QC
9300	SYY GTMDIKKINE GLLDSKILSA FNTVIALLGS	NiVG protein
	IVIIVMNIMI IQNYTRSTDN QAVIKDALQG	attachment
	IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT	glycoprotein
	IPANIGLLGS KISQSTASIN ENVNEKCKFT	Truncated Δ25
	LPPLKIHECN ISCPNPLPFR EYRPQTEGVS	Without N-terminal
	NLVGLPNNIC LQKTSNQILK PKLISYTLPV	methionine
	VGQSGTCITD PLLAMDEGYF AYSHLERIGS
	CSRGVSKQRI IGVGEVLDRG DEVPSLFMTN
	VWTPPNPNTV YHCSAVYNNE FYYVLCAVST
	VGDPILNSTY WSGSLMMTRL AVKPKSNGGG
	YNQHQLALRS IEKGRYDKVM PYGPSGIKQG
	DTLYFPAVGF LVRTEFKYND SNCPITKCQY
	SKPENCRLSM GIRPNSHYIL RSGLLKYNLS
	DGENPKVVFI EISDQRLSIG SPSKIYDSLG
	QPVFYQASFS WDTMIKFGDV LTVNPLVVNW
	RNNTVISRPG QSQCPRENTC PEICWEGVYN
	DAFLIDRINW ISAGVELDSN QTAENPVFTV
	FKDNEILYRA QLASEDINAQ KTITNCFLLK
	NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC
9301	TMDIKKINE GLLDSKILSA FNTVIALLGS	NiVG protein
	IVIIVMNIMI IQNYTRSTDN QAVIKDALQG	attachment
	IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT	glycoprotein
	IPANIGLLGS KISQSTASIN ENVNEKCKFT	Truncated Δ30
	LPPLKIHECN ISCPNPLPER EYRPQTEGVS	Without N-terminal
	NLVGLPNNIC LQKTSNQILK PKLISYTLPV	methionine
	VGQSGTCITD PLLAMDEGYF AYSHLERIGS
	CSRGVSKQRI IGVGEVLDRG DEVPSLEMTN
	VWTPPNPNTV YHCSAVYNNE FYYVLCAVST
	VGDPILNSTY WSGSLMMTRL AVKPKSNGGG
	YNQHQLALRS IEKGRYDKVM PYGPSGIKQG
	DTLYFPAVGF LVRTEFKYND SNCPITKCQY
	SKPENCRLSM GIRPNSHYIL RSGLLKYNLS
	DGENPKVVFI EISDQRLSIG SPSKIYDSLG
	QPVFYQASFS WDTMIKFGDV LTVNPLVVNW
	RNNTVISRPG QSQCPRENTC PEICWEGVYN
	DAFLIDRINW ISAGVELDSN QTAENPVFTV
	FKDNEILYRA QLASEDTNAQ KTITNCFLLK
	NKIWCISLVE IYDTGDNVIR PKLFAVKIPE QC
9302	KKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI	NiVG protein
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	attachment
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	glycoprotein
	KISQSTASIN ENVNEKCKFT LPPLKIHECN	Truncated and
	ISCPNPLPFR EYRPQTEGVS NLVGLPNNIC	mutated
	LQKTSNQILK PKLISYTLPV VGQSGTCITD	(E501 A, W504A,
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI	Q530A, E533A) NIV G
	IGVGEVLDRG DEVPSLFMTN VWTPPNPNTV	protein (Gc Δ 34)
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY	Without N-terminal
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS	methionine
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PAICAEGVYN DAFLIDRINW
	ISAGVFLDSN ATAANPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QCT
9303	MADSKLVSL NNNLSGKIKD QGKVIKNYYG	Hendra virus G protein
	TMDIKKINDG LLDSKILGAF	Uniprot O89343
	NTVIALLGSI IIIVMNIMII QNYTRTTDNQ	Without N-terminal
	ALIKESLQSV QQQIKALTDK IGTEIGPKVS	methionine
	LIDTSSTITI PANIGLLGSK ISQSTSSINE
	NVNDKCKFTL
	PPLKIHECNI SCPNPLPFRE YRPISQGVSD
	LVGLPNQICL QKTTSTILKP RLISYTLPIN
	TREGVCITDP LLAVDNGFFA YSHLEKIGSC
	TRGIAKQRII GVGEVLDRGD KVP SMFMTNV
	WTPPNPSTIH HCSSTYHEDF YYTLCAVSHV
	GDPILNSTSW TESLSLIRLA VRPKSDSGDY
	NQKYIAITKV ERGKYDKVMP
	YGPSGIKQGD TLYFPAVGFL PRTEFQYNDS
	NCPIIHCKYS KAENCRLSMG
	VNSKSHYILR SGLLKYNLSL GGDIILQFIE
	IADNRLTIGS PSKIYNSLGQ PVFYQASYSW
	DTMIKLGDVD TVDPLRVQWR NNSVISRPGQ
	SQCPRFNVCP
	EVCWEGTYND AFLIDRLNWV SAGVYLNSNQ
	TAENPVFAVF KDNEILYQVP LAEDDINAQK
	TITDCFLLEN VIWCISLVEI YDTGDSVIRP
	KLFAVKIPAQ CSES
9304	KKINEGLLDSKILSA FNTVIALLGS IVIIVMNIMI	NiVG protein
	IQNYTRSTDN QAVIKDALQG IQQQIKGLAD	attachment
	KIGTEIGPKV SLIDTSSTIT IPANIGLLGS	glycoprotein
	KISQSTASIN ENVNEKCKFT LPPLKIHECN	Truncated (Gc Δ 34)
	ISCPNPLPER EYRPQTEGVS NLVGLPNNIC	Without N-terminal
	LQKTSNQILK PKLISYTLPV VGQSGICITD	methionine
	PLLAMDEGYF AYSHLERIGS CSRGVSKQRI
	IGVGEVLDRG DEVPSLFMIN VWTPPNPNTV
	YHCSAVYNNE FYYVLCAVST VGDPILNSTY
	WSGSLMMTRL AVKPKSNGGG YNQHQLALRS
	IEKGRYDKVM PYGPSGIKQG DTLYFPAVGF
	LVRTEFKYND SNCPITKCQY SKPENCRLSM
	GIRPNSHYIL RSGLLKYNLS DGENPKVVFI
	EISDQRLSIG SPSKIYDSLG QPVFYQASFS
	WDTMIKFGDV LTVNPLVVNW RNNTVISRPG
	QSQCPRENTC PEICWEGVYN DAFLIDRINW
	ISAGVFLDSN QTAENPVFTV FKDNEILYRA
	QLASEDTNAQ KTITNCFLLK NKIWCISLVE
	IYDTGDNVIR PKLFAVKIPE QCT
9305	LSQLQKNYLDNSNQQGDKMNNPDKKLSVNFNPLELDKGQK	gb: JQ001776:8170-
	DLNKSYYVKNKNYNVSNLLNESLHDIKFCIYCIFSLLIII	10275|Organism: Cedar
	TIINIITISIVITRLKVHEENNGMESPNLQSIQDSLSSLT	virus|Strain
	NMINTEITPRIGILVTATSVTLSSSINYVGTKTNQLVNEL	Name: CG1a|Protein
	KDYITKSCGFKVPELKLHECNISCADPKISKSAMYSTNAY	Name: attachment
	AELAGPPKIFCKSVSKDPDFRLKQIDYVIPVQQDRSICMN	glycoprotein|Gene
	NPLLDISDGFFTYIHYEGINSCKKSDSFKVLLSHGEIVDR	Symbol: G Without N-
	GDYRPSLYLLSSHYHPYSMQVINCVPVTCNQSSFVFCHIS	terminal methionine
	NNTKTLDNSDYSSDEYYITYFNGIDRPKTKKIPINNMTAD
	NRYIHFTFSGGGGVCLGEEFIIPVTTVINTDVFTHDYCES
	FNCSVQTGKSLKEICSESLRSPINSSRYNLNGIMIISQNN
	MTDFKIQLNGITYNKLSFGSPGRLSKTLGQVLYYQSSMSW
	DTYLKAGFVEKWKPFTPNWMNNTVISRPNQGNCPRYHKCP
	EICYGGTYNDIAPLDLGKDMYVSVILDSDQLAENPEITVF
	NSTTILYKERVSKDELNTRSTTTSCFLFLDEPWCISVLET
	NRFNGKSIRPEIYSYKIPKYC
9306	PQKTVEFINMNSPLERGVSTLSDKKTLNQSKITKQGYFGL	gb: NC_025256:9117-
	GSHSERNWKKQKNQNDHYMTVSTMILEILVVLGIMENLIV	11015|Organism: Bat
	LTMVYYQNDNINQRMAELISNITVLNLNLNQLINKIQREI	Paramyxovirus
	IPRITLIDTATTITIPSAITYILATLTTRISELLPSINQK	Eid_hel/GH-
	CEFKTPTLVLNDCRINCTPPLNPSDGVKMSSLATNLVAHG	M74a/GHA/2009|Strain
	PSPCRNFSSVPTIYYYRIPGLYNRTALDERCILNPRLTIS	Name: BatPV/Eid_hel/
	STKFAYVHSEYDKNCTRGFKYYELMTFGEILEGPEKEPRM	GH-
	FSRSFYSPTNAVNYHSCTPIVTVNEGYFLCLECTSSDPLY	M74a/GHA/2009|Protein
	KANLSNSTFHLVILRHNKDEKIVSMPSFNLSTDQEYVQII	Name: glycoprotein|Gene
	PAEGGGTAESGNLYFPCIGRLLHKRVTHPLCKKSNCSRID	Symbol: G Without
	DESCLKSYYNQGSPQHQVVNCLIRIRNAQRDNPTWDVITV	N-terminal methionine
	DLTNTYPGSRSRIFGSFSKPMLYQSSVSWHILLQVAEITD
	LDKYQLDWLDTPYISRPGGSECPFGNYCPTVCWEGTYNDV
	YSLTPNNDLFVTVYLKSEQVAENPYFAIFSRDQILKEFPL
	DAWISSARTTTISCFMFNNEIWCIAALEITRLNDDIIRPI
	YYSFWLPTDCRTPYPHTGKMTRVPLRSTYNY
9307	ATNRDNTITSAEVSQEDKVKKYYGVETAEKVADSISGNKV	gb: NC_025352:8716-
	FILMNTLLILTGAIITITLNITNLTAAKSQQNMLKIIQDD	11257|Organism:
	VNAKLEMFVNLDQLVKGEIKPKVSLINTAVSVSIPGQISN	Mojiang virus|Strain
	LQTKFLQKYVYLEESITKQCTCNPLSGIFPTSGPTYPPTD	Name: Tongguan1|
	KPDDDTTDDDKVDTTIKPIEYPKPDGCNRTGDHFTMEPGA	Protein Name:
	NFYTVPNLGPASSNSDECYINPSFSIGSSIYMFSQEIRKT	attachment
	DCTAGEILSIQIVLGRIVDKGQQGPQASPLLVWAVPNPKI	glycoprotein|Gene
	INSCAVAAGDEMGWVLCSVTLTAASGEPIPHMEDGFWLYK	Symbol: G Without N-
	LEPDTEVVSYRITGYAYLLDKQYDSVFIGKGGGIQKGNDL	terminal methionine
	YFQMYGLSRNRQSFKALCEHGSCLGTGGGGYQVLCDRAVM
	SFGSEESLITNAYLKVNDLASGKPVIIGQTFPPSDSYKGS
	NGRMYTIGDKYGLYLAPSSWNRYLRFGITPDISVRSTTWL
	KSQDPIMKILSTCTNTDRDMCPEICNTRGYQDIFPLSEDS
	EYYTYIGITPNNGGTKNFVAVRDSDGHIASIDILQNYYSI
	TSATISCFMYKDEIWCIAITEGKKQKDNPQRIYAHSYKIR
	QMCYNMKSATVTVGNAKNITIRRY
9308	DFDKLNKIGVVQGRVLNYKIKGDPMTKDLVLKFIPNIVNI	gb: JQ001776:6129-
	TECVREPLSRYNETVRRLLLPIHNMLGLYLNNTNAKMTGL	8166|Organism: Cedar
	MIAGVIMGGIAIGIATAAQITAGFALYEAKKNTENIQKLT	virus|Strain
	DSIMKTQDSIDKLTDSVGTSILILNKLQTYINNQLVPNLE	Name: CG1a|Protein
	LLSCRQNKIEFDLMLTKYLVDLMTVIGPNINNPVNKDMTI	Name: fusion
	QSLSLLFDGNYDIMMSELGYTPQDFLDLIESKSITGQIIY	glycoprotein|Gene
	VDMENLYVVIRTYLPTLIEVPDAQIYEFNKITMSSNGGEY	Symbol: F (without
	LSTIPNFILIRGNYMSNIDVATCYMTKASVICNQDYSLPM	signal sequence)
	SQNLRSCYQGETEYCPVEAVIASHSPRFALINGVIFANCI
	NTICRCQDNGKTITQNINQFVSMIDNSTCNDVMVDKFTIK
	VGKYMGRKDINNINIQIGPQIIIDKVDLSNEINKMNQSLK
	DSIFYLREAKRILDSVNISLISPSVQLFLIIISVLSFIIL
	LIIIVYLYCKSKHSYKYNKFIDDPDYYNDYKRERINGKAS
	KSNNIYYVGD
9309	SRALLRETDNYSNGLIVENLVRNCHHPSKNNLNYTKTQKR	gb: NC_025256:6865-
	DSTIPYRVEERKGHYPKIKHLIDKSYKHIKRGKRRNGHNG	8853|Organism: Bat
	NIITIILLLILILKTQMSEGAIHYETLSKIGLIKGITREY	Paramyxovirus
	KVKGTPSSKDIVIKLIPNVTGLNKCTNISMENYKEQLDKI	Eid_hel/GH-
	LIPINNIIELYANSTKSAPGNARFAGVIIAGVALGVAAAA	M74a/GHA/2009|Strain
	QITAGIALHEARQNAERINLLKDSISATNNAVAELQEATG	Name: BatPV/Eid_hel/
	GIVNVITGMQDYINTNLVPQIDKLQCSQIKTALDISLSQY	GH-
	YSEILTVFGPNLQNPVTTSMSIQAISQSFGGNIDLLLNLL	M74a/GHA/2009|Protein
	GYTANDLLDLLESKSITGQITYINLEHYFMVIRVYYPIMT	Name: fusion
	TISNAYVQELIKISFNVDGSEWVSLVPSYILIRNSYLSNI	protein|Gene
	DISECLITKNSVICRHDFAMPMSYTLKECLTGDTEKCPRE	Symbol: F (without
	AVVTSYVPRFAISGGVIYANCLSTTCQCYQTGKVIAQDGS	signal sequence)
	QTLMMIDNQTCSIVRIEEILISTGKYLGSQEYNTMHVSVG
	NPVFTDKLDITSQISNINQSIEQSKFYLDKSKAILDKINL
	NLIGSVPISILFIIAILSLILSIITFVIVMIIVRRYNKYT
	PLINSDPSSRRSTIQDVYIIPNPGEHSIRSAARSIDRDRD
9310	ILHY EKLSKIGLVK GITRKYKIKS	Hendra virus F protein
	NPLTKDIVIK MIPNVSNVSK CTGTVMENYK	Uniprot O89342
	SRLIGILSPI KGAIELYNNN	(without signal
	THDLVGDVKL AGVVMAGIAI GIATAAQITA	sequence)
	GVALYEAMKN ADNINKLKSS
	IESTNEAVVK LQETAEKTVY VLTALQDYIN
	TNLVPTIDQI SCKQTELALD
	LALSKYLSDL LFVFGPNLQD PVSNSMTIQA
	ISQAFGGNYE TLLRTLGYAT EDFDDLLESD
	SIAGQIVYVD LSSYYIIVRV YFPILTEIQQ
	AYVQELLPVS
	FNNDNSEWIS IVPNFVLIRN TLISNIEVKY
	CLITKKSVIC NQDYATPMTA
	SVRECLIGST DKCPRELVVS SHVPRFALSG
	GVLFANCISV TCQCQTTGRA ISQSGEQTLL
	MIDNTTCTTV VLGNIIISLG KYLGSINYNS
	ESIAVGPPVY
	TDKVDISSQI SSMNQSLQQS KDYIKEAQKI
	LDTVNPSLIS MLSMIILYVL
	SIAALCIGLI TFISFVIVEK KRGNYSRLDD
	RQVRPVSNGD LYYIGT
9311	IHYDSLSKVGVIKGLTYNYKIKGSPSTKLMVVKLIPNIDS	gb: NC_025352:5950-
	VKNCTQKQYDEYKNLVRKALEPVKMAIDTMLNNVKSGNNK	8712|Organism: Mojiang
	YRFAGAIMAGVALGVATAATVTAGIALHRSNENAQAIANM	virus|Strain
	KSAIQNTNEAVKQLQLANKQTLAVIDTIRGEINNNIIPVI	Name: Tongguan1|
	NQLSCDTIGLSVGIRLTQYYSEIITAFGPALQNPVNTRIT	Protein Name: fusion
	IQAISSVENGNFDELLKIMGYTSGDLYEILHSELIRGNII	protein|Gene
	DVDVDAGYIALEIEFPNLILVPNAVVQELMPISYNIDGDE	Symbol: F (without
	WVTLVPRFVLTRTILLSNIDTSRCTITDSSVICDNDYALP	signal sequence)
	MSHELIGCLQGDTSKCAREKVVSSYVPKFALSDGLVYANC
	LNTICRCMDTDTPISQSLGATVSLLDNKRCSVYQVGDVLI
	SVGSYLGDGEYNADNVELGPPIVIDKIDIGNQLAGINQTL
	QEAEDYIEKSEEFLKGVNPSIITLGSMVVLYIFMILIAIV
	SVIALVLSIKLTVKGNVVRQQFTYTQHVP SMENINYVSH
9312	(GGGS)n wherein n is 1 to 10	Peptide linker
9313	GGGGSGGGGSGGGGS	Peptide linker
9314	TTAASGSSGGSSSGA	Peptide linker
9315	GSTSGSGKPGSGEGSTKG	Peptide linker